CHRONICPYELONEPHRITIS ANDARTERIAL HYPERTENSION

By ALLAN M. BUTLER

(From the Department of Pediatrics of the Harvard Medical School and the Infants' andChildren's Hospitals, Boston)

(Received for publication July 7, 1937)

T'he present paper presents certain clinical andpathological evidence which demonstrates that hy-pertension not infrequently is associated withpyelonephritis before there is any appreciable dim-inution in renal function and that hypertensionwhich is secondary to unilateral pyelonephritismay disappear when the involved kidney is re-moved.

Ritter and Baehr (1) described renal arteriolarsclerosis in congenital polycystic disease of thekidney and remarked upon a preliminary periodof arterial hypertension, cardiac hypertrophy andhyposthenuria that usually precedes the terminaluremia in that disease. Bell and Pedersen (2)stated that " hypertension has never been reportedin pyelonephritis." Volhard (3) and Schwarz(4) reported hypertension-in patients with con-tracted kidneys (schrumpfnieren). Longcopeand Winkenwerder (5) reported elevated bloodpressures in the uremic phase of cases of chronicpyelonephritis. Weiss, Parker and Robb (6)observed that patients with malignant hyperten-sion frequently had a history of chronic pyelone-phritis, pyelitis, or perinephritic abscess. Theysuggested that such a renal infection may heal butthat the hypertension in'itiated by it may continueto progress. Fishberg (7) mentioned the hyper-tension that may occur in children in the presenceof urinary obstruction and in polycystic diseaseof the kidney when there is extensive destructionof renal parenfchyma. He stated, however, thathypertension does not occur in that disease if thereare extensive areas of intact parenchyma. Peters(8), Peters, Lavietes and Zimmerman (9), andZimmerman and Peters (10) have called attentionto the frequency with which pyuria and eclampsiaare associated in pregnancy and suggested a re-lation between urinary tract infection and hyper-tension. Kimmelstiel and Wilson (11) studiedthirteen patients with acute diffuse pyelonephritis;nine died in uremia, and hypertension was presentin four of these. Two patients presented what

was interpreted as essential hypertension withsuperimposed diffuse acute pyelonephritis butwithout renal insufficiency. Twenty-six patientswho suffered from diffuse chronic pyelonephritiswere also studied; of these, hypertension anduremia were associated in sixteen; hypertensionalone was present in four, and uremia withouthypertension in six. Hypertension withoutmarked renal insufficiency, therefore, was presentin six of their patients. In the majority of in-stances, they were unable to decide whether theywere dealing with a primary " vascular " hyper-tension or with a secondary " renal " hypertension.

In spite of the frequency with which pyelone-phritis is encountered in childhood (12), we havefound no report of a serious hypertension oc-curring in the pyelonephritis of childhood beforerenal insufficiency was present. Interestinglyenough, Amberg ( 13) in reporting twenty-fivecases of hypertension in children included fivepatients with pyuria or bacilluria but made no par-ticular comment upon the presence of pyelonephri-tis in these patients.

The records concerning the blood pressures ofmany of the patients admitted to this hospital withchronic pyelonephritis are not complete enough tosupply accurate information concerning the re-spective times at which the hypertension, if pres-ent, and renal insufficiency first appeared, but suchdata as are available seem significant. During thepast ten years fifteen children between three andeleven years of age were shown at necropsy tohave pyelonephritis. Adequate records of theblood pressures of seven of these patients are notavailable. The records of the blood pressures forthe remaining eight patients show systolic pres-sures ranging from 250 to 140 mm. Hg and dia-stolic pressures from 170 to 110 mm. Hg, theaverage systolic and diastolic pressures being re-spectively, 190 and 140 mm. Hg. Two of thesepatients (Cases 3 an'd 4 reported below) had hy-pertensive crises and died of cardiac failure before

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significant nitrogen retention occurred. The clini-cal histories of two others of the group studiedpathologically indicated that the pyelonephritisand hypertension preceded severe nitrogen reten-tion. During the same ten year period three pa-tients with pyelonephritis and hypertension diedand permission for autopsy was not obtained.The histories of two of these patients (Cases 1and 2 below) indicate that the pyelonephritis andhypertension preceded significant* renal insuffi-ciency and nitrogen retention. During this same

definite proof that the pyelonephritis preceded thehypertension.

The fifth case reported here is that of a patientwho, coincident with a ureteral calculus, wasfound to have a unilateral pyelonephritis and dur-ing the course of the next 8 months developedhypertension and cardiac failure. The removal ofthe one infected kidney was followed by clearingof the urine and a return of the blood pressure tonormal where it has remained for 20 months.In this case there is strong evidence th-at the pye-

* 9'- Fi [' A#f s,I ts Mbiiz,

FIG. 1.P HOTOMICROGRAPHOF MICROSCOPICSECTION PREPAREDFROMKIDNEY.OF CASE 4

Hematoxylin and eosin. Reduced from a magnification of 240 di-ameters. Note prominence and thickening of walls of small arterioles,interstitial infiltration and casts in the renal tubules. Both chronic pyelo-nephritis and nephrosclerosis were present in the various sections examined.

period nine patients with pyelonephritis and hy-pertension were admitted to the hospital and whenlast seen were living. Of these patients only onehad renal insufficiency, and in this one the pyelo-nephritis and hypertension preceded the appear-ance of the diminished renal function.

Thus we have fifteen patients (six dead andnine living) who have had chronic pyelonephritisand hypertension over a period of years beforethere was appreciable diminution in kidney func-tion. The detailed records of four of these pa-tients are given below. In these cases there is no

lonephritis preceded the hypertension and in someway had a causal relation to it.

Subsequently, another patient, Case 6, who hada unilateral pyelonephritis and hypertension whichwas relieved by right nephrectomy, and whosehistory suggested a relation between the renallesion and hypertension, was seen on the pediatricward of the Massachusetts General Hospitalthrough the kindness of Dr. Harold Higgins andDr. J. D. Barney.'

1 A full report of this patient will be made by Dr.Barney. It is through his kindness that a brief descrip-tion is given with the cases reported here.

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DISCUSSION

It is of particular interest in relation to the lasttwo patients that A/foritz (14) reported three pa-tients with essential hypertension in each of whomthe renal arteriolar sclerosis was found at ne-cropsy to be limited to one kidney.

Both chronic pyelonephritis and nephrosclerosiswere revealed by postmortem examinations per-formed on two of our patients (Cases 3 an'd 4).The photomicrograph shown in Figure 1 illus-trates the extensive character of the renal ar-teriolar sclerosis in Case 4. From the clinical ex-

tients who suffered from both pyelonephritis andhypertension.

A detailed review of the clinical observationsconcerning the association of pyelonephritis andhypertensioni in patients studied in this hospital,however, led to the hypothesis that the hyperten-sion might well be related to the local effect of thepyelonephritis rather than to the renal insuffici-ency encountered late in the disease. When thishypothesis was put to an empirical test by the re-moval of the infected kidney in a patient whosuffered from unilateral pyelonephritis and hyper-

m

FIG. 2. PHOTOMICROGRAPHOF MICROSCOPIC SECTION PREPAREDFROM THEKIDNEY REMOVEDFROMCASE 5

Hematoxylin and eosin. Reduced from a magnification of 240 di-ameters. Note diffuse pyelonephritis. No thickening of arterioles com-parable to that noted in Case 4 is demonstrable.

amination of the retinal and peripheral vessels itis proable that nephrosclerosis was present in ad-dition to the pyelonephritis in Cases 1 and 2. Itis clear that no conclusion may be drawn from ourevidence in these four cases concerning' the rela-tive time of onset of the pyelonephritis and thenephrosclerosis or their relative importance in theproduction of hypertension. The same difficultywas encountered by Kimmelstiel and Wilsoh ( 11)when they attempted to decide whether they weredealing with primary " vascular " hypertension orwith secondary " renal " hypertension in their pa-

tension (Case 5) it was found to be effective.The results in Dr. Barney's case (Case 6) lendfurther support to such a relation between thepyelonephritis and hypertension.

Pathological examination of the kidney re-moved from our patient, Case 5, showed in ad-dition' to severe pyelonephritis very early sclerosisof the renal arterioles. These vascular lesionswere not sufficiently advanced or prominent tomerit the term of nephrosclerosis as it is ordi-narily understood. The photomicropraph of Fig-ure 2 illustrates the absence in Case 5 of such a

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ALLAN M. BUTLER

renal arteriolar sclerosis as observed in Case 4.It is well known that chronic inflammatory proc-esses of various kinds are accompanied by vas-cular changes in the involved areas. In consider-ing the r6le of ischemia and infections in the pro-duction of hypertension, it is of interest thatParker and Weiss (15) observed arteriolar sclero-sis in the lung in the presence of pulmonary con-gestion and infection. That obstruction to theflow of urine from one kidney may result in a risein blood pressure has been shown by Bell andPedersen (2). Goldblatt, Lynch, Hanzal, andSummerville (16), and Wood and Cash (17)have produced hypertension in dogs by partiallyobstructing the blood supply to one or both kid-neys. Both possibilities may play a r6le in theproduction of the hypertension secondary to py-elonephritis.

The clinical significance of the observations re-ported here is clear. At the present time we haveno explanation as to why some patients withpyelonephritis develop hypertension before renalinsufficiency while some develop it only after therenal damage has become marked, and still othersdie in uremia with very little hypertension. Thisquestion merits and will receive further clinicaland pathological study.

PROTOCOLS

Case 1: M. F. (Hospital Number 194,041), a girl of 9years, came to the hosj4pal September 1935 because of re-current frontal headache and vomiting and urinary fre-quency. The family history was not contributory to thepatient's illness. The past history showed her to havebeen a full term baby whose development was somewhatdelayed. She had mumps and pertussis at 5 years of ageand measles at 8 years. Ever since birth she had unusualfrequency and nocturia. At 5 years of age she began tohave severe headaches coming on every 2 to 3 months andlasting all day. At 7 years of age, vomiting began toaccompany the headaches which became more frequent.During the past year she failed to gain and was fatiguedvery easily. Recently the headaches and vomiting oc-curred weekly. Four months before admission, she wasfound to have pus in her urine and was placed on a keto-genic diet without effect on the pyuria.

A physical examination revealed a thin, chronically ill,mentally alert girl. Both of the fundi showed albu-minuric retinitis; there was edema of the optic discs, andthe retinal arteries were narrowed, tortuous, and gave alight reflex. The heart was enlarged, a roentgenogramshowing a cardiac diameter of 9.8 cm. and an internaldiameter of the chest of 18.5 cm. The aortic arch was

broad. There was a blowing systolic murmur andmarked accentuation of the aortic second sound. Theperipheral arteries were thickened but not beaded. Thesystolic blood pressure was 280 and the diastolic 170 mm.Hg. The right kidney was palpable. The red blood cellcount was 3,700,000 per cu. mm. The hemoglobin was 72per cent. The serum calcium was 9.6 mgm. per cent andthe serum inorganic phosphorus 3.3 mgm. per cent. Theblood urea nitrogen was 35 mgm. per cent and the serumprotein 6.3 grams per cent. An intramuscular phenol-sulphonephthalein test showed 27 per cent excretion in300 cc. of urine in 3 hours. The urea clearance was 17per cent of normal. The urine showed from a very slighttrace to a large trace of albumin and numerous whiteblood cells per high power field.

Two weeks after admission she had a hypertensivecrisis, the blood pressure rising to a systolic of 250 anda diastolic of 210 mm. Hg. She became comatose, de-lirious, and had several convulsions. The urine becamegrossly bloody. A week later she appeared as she did atadmission. Six weeks after admission the blood pressurerose to 260 mm. Hg systolic and 230 mm. Hg diastolic,and she had a generalized convulsion. Twelve days latera right splanchnic nerve resection ,pas done, and afteranother 3 days the left splanchnicd'nerve was resected.Following the second operation she was very anemic andwas given four transfusions. The anemia continued.Eight days later she became oliguric and developed aparotitis and pericardial friction n* and after two moredays died in uremia with a blood nonprotein nitrogen of187 mgm. per cent. Permission for an autopsy was notobtained.

Case 2: B. M. (Hospital Number 110,250), a girl of 8years, entered the hospital in November 1931 because ofrecurrent attacks of headache, fever and vomitingthroughout the previous 18 months. Frequent examina-tion of the urine by the family doctor during this periodhad shown that it always contained pus.

The past history showed she had been a normal babyand had developed normally. She had had measles, per-tussis, and chickenpox. Following tonsillitis at 3 yearsof age she had had a tonsillectomy and adenoidectomy.Immediately before the present illness she had hadmumps.

The physical examination showed a well developed butsmall, undernourished, pale girl who appeared chronicallyill. The significant positive findings follow. The retinalarteries showed increased light reflex, narrowing of thelumen and tortuosity. The disks were blurred and hyper-emic. The heart sounds were loud and forceful. Therewas a soft systolic murmur with a marked accentu-ation of the aortic and pulmonic second sounds. Radialand brachial arteries were thickened. The systolic bloodpressure was 210 mm. Hg and the diastolic 170 mm. Hg.On repeated examination the urine contained a very slighttrace of albumin and 5 to 30 white blood cells per highpower field in uncentrifuged specimens. On culture ofthe urine there was a growth of B. coli. The blood non-protein nitrogen was 24 mgm. per cent. An intramuscu-lar phenolsulphonephthalein test showed 50 per cent ex-

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PYELONEPHRITIS AND HYPERTENSION

cretion in two hours. A urea clearance was 65 per centof normal. A urine concentration test showed an inabil-ity to concentrate above 1.012.2

Two weeks after entry the headaches became more

severe. The following day the patient had a hypertensivecerebral crisis. The blood pressure at this time was 240mm. Hg systolic and 170 mm. Hg diastolic. The patientrecovered from this cerebral accident, and the bloodpressure in the course of the next week fell to 180 mm.

Hg systolic and 150 mm. Hg diastolic. Before an ex-

amination of the urinary tract could be made the parentsremoved the child against our advice.

Case 3: R. E. (Hospital Number 107,386), a boy 7years of age, entered the hospital in January 1933 withthe chief complaint of severe headaches for several years

and vomiting and convulsions during the past 9 months.He was a full term baby born following a normal labor.His early development was normal, except that he grew

slowly, weighing 21 pounds at 2 years of age, 24 poundsat 3 years of age, and 32 pounds at 5 years of age. At2 years of age he was found to have a marked phimosiswhich had caused pain on urination for the past 4 months.At this time there was some tenderness to pressure over

the bladder, and the urine was found to contain a trace ofalbumin, but no white blood cells. A circumcision re-

lieved the painful urination. He had pertussis at 2 years

of age, had broken a wrist in a fall at 5 years of age,and one month before admission had received a blowover the left eye which had caused a hemorrhage into theeye which had been treated at the Boston City Hospital.He had had frequency and nocturia for several years.

During the past 5 months the vomiting was frequentlyprojectile. Two months before admission it was knownthat his systolic blood pressure was 220 mm. Hg.

Physical examination revealed a somewhat underdevel-oped and undernourished boy weighing 37 pounds, whowas mentally alert and in no apparent distress. The sig-nificant positive findings were as follows. Both retinasshowed multiple scarring from old hemorrhages. Theretinal arteries were narrow and the veins unusually tor-tuous. The disk margins were indistinct, and there was

slight papilledema. The radial and brachial arteries were

thickened. The heart was slightly enlarged to the left.The aortic second sound was greatly accentuated. Thesystolic blood pressure was 240 mm. Hg and the diastolicblood pressure, 190 mm. Hg. The liver was 3 cm. belowthe costal margin. The spleen was palpable. Repeatedexamination of the urine showed a slight trace of albuminbut no sediment. The blood nonprotein nitrogen was 30mgm. per cent. Serum calcium and phosphorus were

normal. An intramuscular phenolsulphonephthalein testshowed 32 per cent excretion in 2 hours. The urea clear-ance was 100 per cent of normal. A concentration testshowed the specific gravity to be limited to 1.012.2Roentgenograms of the skull showed definite separationof the coronal and sagittal sutures indicating increased

2 Wehave noted such a discrepancy between the specificgravity and urea clearance tests in several of our patientswith hypertension.

intracranial pressure. Ventriculograms showed no lo-calized distortion or filling defect. The very slight dila-tation of the ventricles was consistent with a cerebraledema. The long bones were negative for lead. The redblood cells showed no stippling. The diagnosis of malig-nant hypertension of unknown etiology was made. Thechild was discharged to a convalescent home on February28th with the same hypertension with which he entered.He died of cardiac failure August 9, 1933, without re-entering the hospital. An autopsy performed outside thehospital 8 showed the following: cardiac hypertrophy anddilatation, sclerosis of aorta, coronary and cerebral ves-sels, bilateral pyelonephritis and hydronephrosis, arteri-olar nephrosclerosis, bilateral hydro-ureters, cystitis anddilatation of the bladder.

Case 4: R. W. (Hospital Number 143,483), an 11year old boy, was admitted to the hospital October 14,1930, because of severe recurrent attacks of frontal head-ache, nausea, and vomiting beginning abruptly 11 monthsago. The attacks occurred about once a week and werefrequently precipitated by emotional disturbances. Inaddition to these symptoms there had been severe upperabdominal pain and dizziness over the past month. Thefamily history was not relevant. The past historyshowed the patient to have been born a healthy child fol-lowing a normal labor. His development was normal.He was reported to have had measles at 2 months ofage, pertussis at 3 years, and repeated attacks of tonsil-litis up to 2 years ago, when his tonsils and adenoidswere removed.

Physical examination revealed a poorly developedslightly underweight child. The blood pressure was260 mm. Hg systolic and 180 mm. Hg diastolic. Theperipheral arteries were thickened. After rest, the bloodpressure varied from 210 to 150 systolic and 160 to 120diastolic. There was an albuminuric retinitis with hemor-rhages and exudate. The heart was not enlarged. Fol-lowing the administration of 0.12 gram of sodium nitriteby mouth the blood pressure fell from 200 systolic and150 diastolic to 155 systolic and 130 diastolic, the handsbecame cold and fingers and face cyanotic, and thebrachial, cubital and radial arteries became softer. Theurine contained from a very faint trace to a trace ofalbumin, moderate and varying numbers of white bloodcells, and occasional hyaline and granular casts. Theurea clearance was 88 per cent of normal and the specificgravity of the urine varied from 1.020 to 1.005.

One month after admission the pain in the left flankbecame severer, the temperature rose to 103° F., thepyuria became more pronounced, and there was local ten-derness and fullness in the left kidney region. The whiteblood count rose to 22,000. It was at this time that thelower blood pressures were observed. An exploratoryoperation was deemed advisable. Through an incisionrunning obliquely forward from the left side of thecostovertebral angle the left kidney was exposed. Thekidney was found to be markedly edematous. Toward

8 Weare indebted to Dr. Williams of the Rhode IslandGeneral Hospital for the autopsy report.

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ALLAN M. BUTLER

the lower pole there was a large amount of cellulitis anda small amount of pus. Nothing was felt in the positionof the adrenal. A drain was inserted to the infectedarea and the wound closed in layers to the drain. Pusdrained from the wound for 10 days. The drain wasthen removed, and the wound healed well. The urinecontinued to show a few white blood cells. The albu-minuric retinitis had now disappeared. After another 10days the blood pressure began gradually to increase untilit had again reached 220 systolic and 175 diastolic. Atthis time the spinal fluid pressure was 350 mm. H20.Intravenous pyelograms showed the dye to be well con-centrated and bilateral enlarged renal pelves and bluntedcalyces. The renal function remained unchanged.

On January 2, 1931, a second exploratory operation wasperformed through a left rectus incision from the costalmargin to umbilicus and a transverse incision from um-bilicus to perpendicular line from anterior superior spine.The right side of the abdomen, right kidney, and supra-renal was explored and nothing abnormal was made out.The peritoneum over the left kidney was incised and re-tracted. There was a moderate amount of inflammationabout the enlarged left kidney. The left adrenal ap-peared normal.

Following the operation, the blood pressure continuedits gradual rise reaching 250 mm. Hg systolic and 180mm. Hg diastolic. At this time he had a hypertensivecrisis with convulsions, pallor of left optic disc, and lossof sight. His heart showed slight left sided hypertrophyand a systolic murmur was heard at the apex. He re-covered, regained his vision, and improved sufficiently tobe discharged home to his family physician. The urinestill showed a trace of albumin, rare white and red bloodcells, epithelial cells and granular casts. The blood non-protein nitrogen was not elevated, the red blood countwas 4,900,000 and hemoglobin 80 per cent. The bloodpressure was 230 mm. Hg systolic and 175 mm. Hg di-astolic.

He was readmitted to the hospital April 17, 1931, withcardiac failure. The blood pressure was 140 mm. Hgsystolic and 100 mm. Hg diastolic. The urea clearanceof 79 per cent was normal. He had repeated attacks ofsevere abdominal pain and dyspnea relieved by obstructingthe venous return from the lower extremities. The car-diac decompensation increased, and he died 10 days afterreadmission.

Postmortem examination (A-31-68) showed bilateralchronic pyelonephritis and marked nephrosclerosis.Streptococcus hemalyticus was recovered from the heart'sblood and from exudate in the right pleural cavity, thepericardial cavity, and the peritoneal cavity. Of particu-lar importance in regard to the clinical story were thefindings in the heart and vascular system, and in thekidneys. The heart was considerably enlarged, moremarked on the left than the right side. On microscopicexamination, diffuse fibrosis of the myocardium wasfound. There was generalized atheromatosis of theaorta. The smaller blood vessels of the pancreas, spleen,and periadrenal tissues were particularly involved. Therewas thickening of both the intima and the media with

definite narrowing of the lumina of these vessels. Con-siderable perivascular fibrosis was also present.

The kidneys were not weighed but appeared definitelyenlarged. They were firm in consistency and were en-closed in strongly adherent and thickened capsules towhich the fibrosed periadrenal tissues were firmly at-tached. On section, the parenchyma was pale, yellowishbrown in color and bulged into the line of incision. Thecortex measured between 4 to 5 mm. in thickness, andwas poorly differentiated from the medulla. No stria-tions or glomeruli could be recognized on the cut surface.The small arteries stood out conspicuously because oftheir thickened walls. The pelves of both kidneys wereslightly dilated. No exudate was present. The ureterswere of uniform caliber and showed no inflammatorychanges grossly.

Five blocks were selected from the kidneys and sectionswere stained by several methods including Mallory's con-nective tissue stain. The main features were severe in-fection and vascular lesions. There was a widespreadchronic and acute inflammatory process with considerablereplacement fibrosis and occasional areas of acute inflam-mation which amounted to abscess formation. In a fewfields, areas of parenchyma were completely necrotic andwere replaced by masses of polymorphonuclear cells.The connective tissue stroma was edematous and was in-filtrated with polymorphonuclear cells in scattered areas.The tubules showed acute degenerative changes. The epi-thelial lining cells were swollen, granular, and often con-tained fat or colloid droplets. Within the lumens of thetubules albuminous precipitate, hyaline and granular castsand cylinders composed of polymorphonuclear leukocyteswere found. The arterioles were markedly thickened,and the lumens were decreased in many cases to the pointof complete obliteration. Often, the walls of the arte-rioles were arranged in concentric rings in the character-istic onion layer arrangement. No hyaline deposits werefound in the walls of the arterioles. The glomerulishowed various degrees of hyalinization of the vasculartufts up to complete hyaline change. Swelling of theendothelial cells with vacuolization was frequently notedin the capillaries of the glomeruli. In occasional areaswhere the acute inflammatory process in the renal paren-chyma was most marked, the tufts of the glomeruli wereinfiltrated with polymorphonuclear leukocytes, and in-flammatory cells and fibrin were occasionally noted inthe capsular spaces. Large numbers of glomeruli, how-ever, retained their normal appearance. (See Figure 1.)

The sequence of events cannot be stated with certainty.There is definite evidence of both old and recent pyelo-nephritis. It is impossible to state whether the arteriolarlesions in the kidney and in other organs of the bodycame before or after the initial infection of the kidneys.The association of vascular lesions of this type andpyelonephritis has been noted on several occasions in ourlaboratory. It should be emphasized, however, that thevascular lesions are not confined to the kidneys; the smallvessels in the pancreas, spleen, and adrenals were alsoinvolved. The enlargement of the heart and the myo-carditis are probably secondary to the vascular disease.

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Case 5: P. B. (Hospital Number 187,522), a boy of 7years, entered the hospital in November 1934 because ofhematuria 3 to 4 times a week for the past two monthsand occasional dysuria. The family history was noncon-tributory. He had had a normal infancy and alwaysbeen well except for chickenpox at 4 months of age,mumps at 2 years and measles at 6 years. Physical ex-amination showed a well developed and nourished boywith no abnormal findings. The blood pressure was 98mm. Hg systolic and 50 mm. Hg diastolic. The urinecontained a slight trace of albumin and was loaded withred blood cells. A roentgenogram of the abdomenshowed a large solitary calculus at the lower pole of theright kidney. Intravenous pyelograms two days latershowed the calculus in the region of the lower end of theright ureter. The right kidney pelvis was considerablydilated and the calyces were blunted. The right ureterwas not outlined. The left kidney pelvis, calyces, andureter were normal. The blood nonprotein nitrogen was20 mgm. per cent. A phenolsulphonephthalein intra-muscular test resulted in 30 per cent excretion in the firsthour and 25 per cent excretion in the second hour. Thefollowing day Dr. W. E. Ladd exposed the lower end ofthe right ureter and removed the calculus. On analysis,73 per cent of the dry material was ash composed of cal-cium oxalate, carbonate, and phosphate. Retrograde py-elography showed a markedly dilated right kidney pelviswith blunted calyces and a large tortuous right ureter.Culture of the urine from the left ureter and bladdergave no growth. The urine cleared, and the child wasdischarged to the outpatient department.

In January 1935, the urine contained many white bloodcells and culture showed a growth of B. coli. In spite ofhexamethylenamine, ammonium chloride and ketogenicdiet therapy the pyuria and bacilluria continued. OnApril 5, a right nephrostomy was done by Dr. W. E.Ladd. At the lower pole of the kidney the fat was ab-normally adherent, and there were several aberrant ves-

sels, which did not, however, appear to compress theureter. The pelvis of the kidney was greatly dilated andits wall thickened, and the ureter was markedly dilatedand kinked on itself at the level of the lower pole of thekidney. An incision was made in the surface of the kid-ney pelvis, and catheter introduced down into the ureter.The kinking of the latter was partially relieved by free-ing dense, fibrous tissue, and the catheter could then bepassed without difficulty the whole length of the ureter.A silk purse string suture was then placed in the midpoint of the convexity of the kidney, and by sharp andblunt dissection a hole was made through the cortex ofthe kidney into the pelvis. A large catheter was insertedthrough this and carried out through the original inci-sion. The renal cortex was much thicker than antici-pated.

On April 25, a phenolsulphonephthalein intramusculartest showed 15 per cent excretion from the nephrostomydrain in 32 cc. in the first hour and 10 per cent in 26 cc.the second hour. The catheter was removed April 30,the waund healed well, and the patient was discharged

home May 13 with numerous white blood cells in theurine specimens.

On August 7 he still had pyuria. He was readmittedto the hospital on August 13 because of vomiting andrapid pulse for 5 days. The temperature was normal.He was cyanotic and dyspneic with respirations 48 andpulse 140 per minute. The liver was enlarged to theumbilicus and there was dependent edema. The heartwas large, the diameter measuring 13.5 cm. as comparedto an internal diameter of the chest of 21.4 cm. Aus-cultation of the heart showed dropped beats. The bloodpressure was 130 mm. Hg systolic and 100 mm. Hg di-astolic. There had never been any history suggestingrheumatic fever or any acute infection other than thepyelonephritis. After digitalization the pulse rate re-turned to normal, the dropped beats disappeared, therewas a marked diuresis with loss of edema, and the bloodpressure rose to 160 mm. Hg systolic and 105 mm. Hgdiastolic. Urine from the right kidney contained B. coliand pus, and showed a 3 per cent excretion of intramus-cularly injected phenolsulphonephthalein in one hour,while the left kidney gave 16 per cent excretion and noorganisms on culture. A urine concentration test gave aspecific gravity as high as 1.024. The blood nonproteinnitrogen was 24 mgm. per cent. The sedimentation ratewas normal. As there had been no hematuria or cylin-druria characteristic of nephritis at any time during thisadmission and no drop in blood pressure with the diuresis,it was felt that an acute hemorrhagic nephritis on top ofthe pyelonephritis could not account for the elevatedblood pressure. No source of infection other than theright pyelonephritis could be found. During the follow-ing seven weeks the blood pressure varied between 122 to168 systolic and 90 to 110 diastolic. For the specific pur-pose of checking the hypertension and cardiac involve-ment, a right nephrectomy was done by Dr. W. E. Laddon October 5. The ureter was found to be greatly di-lated, tortuous, and to be covered with numerous firmfibrous adhesions. About two inches above the bladder,the ureter regained its normal appearance, so at thispoint it was clamped, ligated, and cut with cautery.

Examination of the right kidney and ureter showed thefollowing. The gross specimen consisted of a right kid-ney measuring approximately 10 X 6 X 3 cm., surroundedby a moderate amount of deep orange-colored perirenalfat. The capsule was thick, opaque, and in certain areasmarkedly adherent to the kidney surface. The externalsurface was a diffuse yellowish-brown in color, stippledwith closely placed deep red punctate areas. Over theinferior pole was a large, irregular, slightly depresseddull purplish-red area to which the capsule was markedlyadherent. At the superior pole were smaller discretesimilar areas averaging 0.3 cm. in diameter. The kidneywas moderately firm but boggy and cut with ease reveal-ing poorly defined cortical and medullary zones. Thecortex was slightly swollen, measuring approximately0.7 cm. in thickmess, slightly irregular, generally paleyellowish-brown in color with faint pinkish-gray linear

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ALLAN M. BUTLER

radiations. At the superior pole there was a dull, moist,purplish-red, wedge-shaped lesion with a deep red centralarea, extending to the tip of an inferior calyx. Themedulla was moist, pale brownish-yellow in color withfaint red linear radiations. The pyramids were pale yel-lowish-brown, smooth and moist. The pelves and calyceswere greatly dilated with moist, rough granular mucosalsurfaces, dirty bluish-yellow in color flecked with nu-merous small bright and dark red pin-point lesions. Theureter was dilated, measuring 2.8 cm. in circumference.It was redundant and kinked but patent. The mucosawas swollen, thickened, wrinkled, and dirty yellowish-gray in color. Numerous small irregular bright red pin-point lesions were scattered over the mucosal surface.The specimen was sectioned and fixed in Zenker's solutionand 10 per cent Formalin solution.

Six sections of kidney and two sections of ureter werestained by various methods including Mallory's connectivetissue stain. There was some thickening, edema, andlymphocytic infiltration of the capsule. The interstitialtissues were densely infiltrated by lymphocytes, poly-morphonuclear leukocytes, and mononuclear cells. Inoccasional areas the renal parenchyma was replaced bypolymorphonuclear leukocytes and lymphocytes. In otherareas, lymphocytes were packed so densely that a sug-gestion of lymph follicle formation was noted. Inflam-matory changes extended throughout the entire kidneyand were prominent in the subpelvic tissues. The con-voluted and collecting tubules were dilated, and the liningepithelium showed cloudy swelling, fragmentation of thecytoplasm, and in some areas flattening of the epithelium.Occasional tubules were filled with polymorphonuclearleukocytes. In many of the glomeruli there was increasedprominence of the basement membrane both in the capil-lary loops and in the capsule itself. Many glomeruliwere practically bloodless. The basement membrane wasparticularly thickened in the areas of greatest inflam-matory infiltration, and the capsules of the glomerulishowed fibrosis and hyalinization. In a number of in-stances there were adhesions between the glomerulartufts and the capsule. Inflammatory cells in the glomeruliwere lacking. Moderate thickening of both the mediaand intima of the smaller arterioles was noted. Edema,acute and chronic inflammation, and congestion werenoted beneath the mucosa of the ureters. (See Figure 2.)

Postoperatively the blood pressure fell to 100 mm. Hgsystolic and 70 mm. Hg diastolic, and the urine was clear.During the subsequent 20 months, examination at sixoutpatient visits have shown that the heart has been ofnormal size, the urine negative for pus and bacteria, theblood pressure never higher than 115 mm. Hg systolicand 75 mm. Hg diastolic, and the urea clearance withinnormal limits.

Case 6: Dr. J. D. Barney's patiet. A girl 10 years ofage with a history of pyuria of at least two years' dura-tion was admitted to the hospital March 1937 with a bac-illuria and a varying number of white blood cells in theurine and a hypertension of 190 mm. Hg systolic and120 mm. Hg diastolic pressure. The blood nonprotein

nitrogen and the excretion of phenolsulphonephthaleinwere within normal limits. The day following the re-moval of the right kidney by Dr. Barney the blood pres-sure fell to 110 mm. Hg systolic and 70 diastolic andremained below that level during the subsequent stay inthe hospital. Three months later, when the child waslast seen, she appeared to be a healthy active child, andthe blood pressure was 92 systolic and 60 diastolic. Dr.T. B. Mallory described the kidney as a small irregularlyscarred kidney with dilated pelvis and slightly injectedureter, which on section showed a most marked thicken-ing of the media and intima of the arterioles and an in-filtration of cells in areas throughout the parenchyma andbeneath the epithelium of the pelvis and several calyces.

I wish to acknowledge my indebtedness to Dr. SidneyFarber for the pathological descriptions of Cases 4 and5 and for his cooperation in reviewing with me manycases of pyelonephritis, and to thank Dr. J. D. Barneyand Dr. T. B. Mallory for permitting reference to theircase.

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