Talk:Paper - Polycystic disease of the kidney (1927)

POLYCYSTIC DISEASE OF THE KIDNEY. By GEORGE MORRIS PIERSOL, M_.D., PHILADELPHIA, PENNSYLVANIA.

Although polycystic degeneration of the kidneys cannot be looked upon as a rare disease, it may be regarded as relatively uncommon. Therefore, it seems justifiable to add to the group of reported cases.

The frequency with which polycystic disease occurs may be judged from the following statistics. In 1887 Naumann? reported fourteen bilateral and two unilateral cases in 10,177 necropsies. Preitz in 1905, working up the Kiel Institute material, found sixteen cases in 10,000 autopsies. Bugbee and Wolstein,? in 4,903 autopsies on children, recorded twenty cases. In 1927 Gruber at Jena collected eight bilateral cases in 3,500 post mortem examinations. During the past three years only five instances of the condition have been found in the necropsy material at the Philadelphia General Hospital. At the Boston City Hospital, Garceau met with ten cases in 2,439 necropsies. A few years ago Barnett was able to collect a total of 251 cases. Since then 238 additional cases have been recorded. An idea of the frequency with which polycystic disease of the kidney is met in our large general city hospitals may be gained from a statement made by Atonna and Morrissey® that during the four years from 1922 to 1926 inclusive the total number of cases reported from the hospitals of New York City averaged only eight per year.

Two striking examples of this disease recently encountered awakened our interest in this condition.

The first case was that of an Irish laborer aged 42 years, admitted during the winter of 1927 to the writer’s service at the Philadelphia General Hospital. His outstanding symptoms were swelling of the abdomen, pain in the left upper abdominal quadrant, swelling of the legs, cough and dyspnoea.

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The patient stated that he had always been unusually well until August, 1926, when he developed acute abdominal pain, was taken to a hospital in Philadelphia, where his appendix was removed. From that time on he had been sick, complaining of the above noted symptoms. His strength failed so that for the four months prior to admission he was unable to work. He had also developed since his operation a decided nocturia.

Aside from the fact that he had been for years a heavy drinker, there was nothing significant in his previous medical or social history. His family history was also unimportant. There was nothing to suggest the existence of polycystic kidneys in any of his forebears.

It is interesting to note that a report on his operation in August, 1926, from the hospital where it was performed, states that a somewhat inflamed appendix was removed, that his liver was enlarged, contained multiple cysts, the lower border being four to five inches below the costal margin. The appendix was removed, and an hepatic cyst was punctured and drained. The patient made a fair recovery and was discharged with a diagnosis of hepatic cyst; impending cirrhosis of the liver.

The salient features of our physical examination of this patient were as follows:

The patient was a well-developed, but rather poorly nourished white male. There was a left peripheral facial palsy due to a severe head injury in 1920. The lungs were normal except for some crackling rales at the right base. There was a distinct widening of the costal angle due to the marked outward flare of the lower ribs as from pressure. The apex beat was visible and palpable in the fifth interspace on the left midaxillary line. Percussion showed decided left sided cardiac enlargement. The aortic second sound was louder than the pulmonic. At the apex a soft, non-transmitted systolic murmur was heard.

Chief interest centered in the abdomen. There was distinct bulging of the left side of the abdomen and of the left flank. A marked ventral hernia was present. The liver was enlarged, hard, non-tender and was palpable two inches below the costal border. The left side of the abodmen was filled with a large, hard, irregular, tender mass. This mass extended down to the left iliac crest and toward the POLYCYSTIC DISEASE OF THE KIDNEY 223

midline to within two inches of the umbilicus. It moved with respiration, was definitely palpable bi-manually, and caused marked fullness in the left flank.

A summary of the laboratory examinations is, viz.: Urine, acid,

clear, sp. gr. 1006-1010. All specimens contained definite traces of albumin. Glucose was always negative. Microscopically no casts were found, but leucocytes and a few red blood cells were always present. : On admission his haemoglobin was 55%; red blood cells 2,950,000; leucocytes 7,200; polymorphonuclears 76% ; lymphocytes 24%. In several subsequent differential counts the eosinophiles were increased, ranging from 2 to 5 per cent.

His blood Wassermann was negative to all antigens. His blood sugar was 155 mgms. per 100 cc. of blood. The urea nitrogen was 40 mgms. per 100 cc. of blood. On the day of admission his temperature was normal, his pulse slightly increased, and his systolic blood pressure 130, diastolic 60.

A tentative diagnosis of cirrhosis of the liver, or Banti’s disease was made.

Three days after admission the patient had a generalized convulsion, epileptiform in character. After this he became toxic, semistuporous, and vomited repeatedly. There was no hematemesis. He became obstinately constipated. His toxemia improved, but the vomiting, especially after taking food, continued. Pain in the left side of the abdomen increased and the mass became larger and felt more nodular.

With the thought of gastrointestinal malignancy in mind, a fractional gastric analysis was done. This showed a total absence of free hydrochloric acid, but no blood. A fluoroscopic examination of the gastrointestinal tract showed no organic lesion of the stomach, which was displaced to the right, but a herring bone appearance of the jejunum, thought to be due to either pressure of adjacent organs or an obstructive lesion at the jejuno-iliac junction.

Inasmuch as the vomiting continued and the patient’s condition was growing steadily weaker, a surgical consultation was held and surgical intervention advised.

An exploratory laparotomy was done under nitrous oxide anas224 GEORGE MORRIS PIERSOL

thesia. The liver, spleen and gall bladder were found normal. The abdomen was found almost filled by two large retroperitoneal polycystic masses. In spite of nine months of varied observation the correct diagnosis of congenital, bilateral, polycystic kidneys was then made for the first time.

Within twenty-four hours after operation the patient died of bronchopneumonia with pulmonary oedema. An autopsy was performed. The essential findings at autopsy were as follows:

The heart was moderately enlarged due to left ventricular hypertrophy. The mitral valve was normal. The coronary arteries showed a slight degree of arteriosclerosis. The aorta showed a moderate degree of arteriosclerosis.. Both lungs were the seat of old pleural adhesions and of recent congestion, oedema and bronchopneumonia. When the abdomen was opened a striking picture was presented. Both kidneys were seen to be markedly enlarged and cystic. They occupied most of the abdominal cavity. Each kidney extended from the pelvis brim to the dome of the diaphragm. The left kidney weighed 1,450 gms., and measured 33 x 18 x 13 cm. The enormously enlarged kidney was made up of innumerable cysts of varying size. The largest cyst measured 5 x 6 cm. in diameter. The right kidney weighed 2,970 gms., was fully as large as its fellow and was identical in structure, being largely converted into a mass of various sized cysts. Upon section little normal renal structure remained in either kidney, the normal parenchyma being largely replaced or compressed by the multiple cysts.

The spleen was somewhat enlarged, soft and congested. The adrenals were plastered on to the upper poles of the kidneys and appeared quite normal. The liver was about normal in size, weighing 2,050 gms. Its capsule was smooth, the lower margin fairly sharp. On section two small cysts were revealed, each about 1.5 cm. in diameter, with thin walls and containing clear fluid. The remainder of the gastrointestinal tract was negative.

The final anatomical diagnosis was: congenital polycystic kidneys; cysts of the liver; moderate arteriosclerosis, and an hypertrophied heart.

The autopsy clearly proved that the masses which had been palpated during life and were regarded as an enlarged liver and POLYCYSTIC DISEASE OF THE KIDNEY 225

spleen, were actually the two large polycystic kidneys. The liver and spleen were never palpable.

In this case a correct clinical diagnosis was never made until after exploratory operation. We failed to interpret correctly the abdominal signs. We overlooked the possible significance of the hypertrophied left ventricle, the accentuated aortic second sound, and the evidence of arteriosclerosis. Our minds were so fixed on other diagnoses that no one gave proper weight to the persistent albuminuria, the occasional red cells in the urine, or the definitely increased blood urea nitrogen. If these findings that pointed to kidney involvement had been given due consideration the existence of renal tumors might have been suspected and proved by pyelography and functional kidney tests.

The second case occurred upon the service of my associate, Dr. H. L. Bockus, at the Hospital of the Graduate School of Medicine of the University of Pennsylvania. I am indebted to Dr. Bockus for the opportunity to study and report this case.

The patient was a business man, aged 64 years, who was admitted on 11-14-1926 as a suspected case of pernicious anemia or carcinoma of the intestinal tract. His chief complaints were weakness, nausea, vomiting, loss of weight and anemia. For eighteen months he had had gastrointestinal symptoms, with the exception of one attack of alleged renal colic in August, 1925. This cleared up and he had no further renal symptoms. Three months before admission his nausea and vomiting became persistent. He lost weight and complained of numbness and tingling in the extremities.

On admission the outstanding features of his physical examination were marked pallor, a definite mouth infection, infected tonsils, a chronic glossitis, marked left ventricular hypertrophy, an accentuated aortic second sound, palpable vessels and decreased knee jerks. The abdomen was soft and relaxed. The liver and spleen were not palpable. On the right side of the abdomen, along the line of the ascending colon and clearly not connected with the liver, was a mass the size of a small apple lying rather superficially and easily palpable. At the time this was looked upon as a carcinoma of the colon.

The laboratory findings soon put a different aspect on this case. On admission his systolic blood pressure was 218, diastolic 165. The 226 GEORGE MORRIS PIERSOL

urine had a specific gravity varying from 1008-1010, contained a heavy cloud of albumin, but no glucose and no casts nor red blood cells. The haemoglobin was 32, erythrocytes 1,900,000, and leucocytes 5,300, with a color index of 0.8. Polymorphonuclears 87%, lymphocytes 11%, transitionals 2%. There were no unrelated red cells nor any blood findings suggestive of true Addisonian anemia. The blood Wassermann was negative to all antigens. The first blood chemistry showed the blood sugar to be 87 mgms. per 100 cc.; uric acid 3.5 mgms.; creatinin 14 mgms.; urea nitrogen 160 mgms.; cholesterol 130 mgms., and chlorides 496 mgms. A subcutaneous phenolsulphonaphthalein test showed no dye eliminated. Later when the dye was injected intravenously, 123% per cent were recovered at the end of the first hour, and a like amount at the end of the second hour. A fractional gastric analysis showed normal gastric function, free hydrochloric acid being present in considerable quantity. An X-ray study showed a dilated aorta, a normal stomach and small intestines, and a colon pushed down by a mass that was obviously not related to the bowel.

The blood findings and gastrointestinal studies clearly eliminated the possibilities of pernicious anemia or intestinal malignancy. All the clinical and laboratory findings pointed clearly to renal insufficiency in a chronic nephritic with hypertension.

Further progress of the case bore this out. The patient became progressively more anemic and weaker. Five days after admission he was stuporous, had a uremic odor to his breath, and his blood urea nitrogen was up to 164 mgms. per 10 cc.; creatinin 30.4 mgms., and the CO, of the plasma equaled 27 vol. %. A transfusion was done with little success at this time. He continued to become more toxic and died in uremia three weeks after admission. Three days before death his creatinin was 21.1 mgms. and his urea nitrogen was up to 170 mgms. per 100 cc. of blood.

During the entire course of his illness the mass in the right upper abdomen was constantly palpable and a less distinct mass could at times be felt on the left side. A week before death he was seen by Dr. J. B. Carnett in consultation, who suggested the diagnosis of bilateral polycystic disease of the kidneys because of the somewhat cystic feel of the right-sided mass, the exclusion of all other POLYCYSTIC DISEASE OF THE KIDNEY 227

explanations for the abdominal masses, and the co-existence of hypertension and renal insufficiency.

The significant features of the autopsy in this case were: Healed tuberculous lesions with adherent pleura at the apices of the lungs with terminal congestion and oedema. There was slight cardiac hypertrophy with chronic fibrous interstitial tissue increase. The gastrointestinal tract was negative. The liver was not enlarged, but contained a few small cysts. The spleen was not enlarged, but was the seat of chronic fibrosis. The masses felt were a pair of definitely enlarged, congenital polycystic kidneys. The right kidney weighed 1,095 gms., the left kidney 890 gms. Both kidneys contained innumerable cysts of varied size. These cysts were lined with low cuboidal and even flattened epithelium. The tissue between the cysts contained Malpighian bodies and tubules, and was the seat of chronic interstitial nephritis.

The fluid from the cysts examined post mortem was slightly turbid and contained non-congerable nitrogen fractions in the following amounts: Uric acid, 20 mgms. per 100 cc.; urea nitrogen, 300 mgms. per 100 cc., and creatinin, 58 mgms. per 100 cc.

In this second case the evidence of renal involvement was much more definite than in the first, but the abdominal tumors were much less obtrusive. As in the first patient the original diagnosis was wrong, and it remained for a surgeon to make a correct one.

Polycystic degeneration of the kidneys may be roughly divided into four groups:

1st. Those in which the condition develops at or shortly after birth. These children die promptly after birth. In this group the condition is usually associated with other developmental defects as cleft palate, imperforate anus, cysts of the ovary, supernumerary digits, etc. In the other groups the condition does not manifest itself until adult life.

2nd. The second group presents nothing that suggests the existence of polycystic kidneys. In this type renal insufficiency develops unexpectedly and is promptly fatal. The true nature of the renal lesion is only discovered at autopsy.

3rd. Group three shows the usual manifestations of chronic hypertensive nephritis often associated with progressive weakness and 228 GEORGE MORRIS PIERSOL

a marked secondary anemia. The polycystic renal degeneration is only recognized when the kidneys become expanded and are definitely palpable cystic tumors. Most of the cases recognized clinically have been in this group. The second case here reported clearly belongs in this class.

4th. The fourth group comprises those cases in which the first symptoms point clearly to urinary tract disease, such as a definite renal tumor, hematuria, renal cells, persistent fullness, pain and dragging in the iliocostal space. These cases are usually recognized more easily and earlier. Our first case more nearly fits into this group.

According to Cabot’s series, the greatest number of cases of polycystic renal degeneration presents symptoms between the fortieth and sixtieth years. The tumors are rarely found after infancy until the eighteenth or twentieth years are passed.

The condition is said to be more common in women than in men. Heredity seems to play a definite rdle in its production. In 1902 Osler reported a family in which the disease occurred repeatedly in different members. Crawford? reported a case in which the disease had occurred with amazing frequency in various members of the patient’s family. He quotes Borelius, and Love and Richmond as having made similar observations.

The condition is more often bilateral than unilateral. Sieber® found only ten unilateral cases in 150 cases proved by autopsy. In adults the most commonly associated pathological conditions are cysts of the liver, arteriosclerosis, and cardiac hypertrophy.

The diagnosis depends largely upon findings in one or both flanks, irregular, nodular tumor formations having the general outline of the kidney. When the renal tumors are bilateral the diagnosis may be made with certainty, as polycystic disease is practically the only cause for bilateral kidney tumors. These tumors may exist for years without symptoms. As a rule, however, albuminuria with other evidences of chronic renal disease develops. Hematuria irregularly intermittent is reported in fifty per cent of cases. When present it is an aid to diagnosis. Pyelography, especially advocated by Atonna and Morrisey,® and functional kidney tests are useful procedures in arriving at a diagnosis. The former is particularly helpful in differenPOLYCYSTIC DISEASE OF THE KIDNEY 229

tiating polycystic disease from -hydronephrosis, pyonephrosis, and hypernephroma. In many cases, especially those in which the tumor is inconspicuous, the diagnosis is difficult and frequently goes unsuspected.

The prognosis in polycystic disease of the kidneys is ultimately uniformly bad. The earlier the age of onset the worse the prognosis. It is rare for adults to survive more than from one to ten years after symptoms develop. The majority of adults succumb in their fourth decade.

The treatment of the condition is thoroughly unsatisfactory and is largely medical. The bilateral nature of the disease makes nephrectomy out of the question. In twenty-two cases nephrectomy was attended by a mortality of 31.89%, and only two cases lived beyond two years. Rovsing’ has advocated puncture and drainage of the cysts for the relief of pressure. His results, however, were of only temporary benefit. Renal infection, urethral obstruction and stone may demand radical surgical interference. On the whole, it is safe to say that the majority of cases will live as long and do as well under palliative medical management.

The pathogenesis of the polycystic kidney has always aroused considerable interest. Virchow held that the uriniferous tubules of the kidney become blocked off as the result of inflammatory tissue in the renal papillae, thus causing true retention cysts. This theory has few, if any, advocates today.

Another group of pathologists contended that the cysts are new growths and that they are virtually cyst-adenomata. Subsequent observations have failed to substantiate this view.

The theory that today is most generally accepted is that the cysts are the outcome of a developmental defect. Recently Kampmeier® has carried on extensive embryological studies on the origin of congenital renal cysts. His conclusions in brief are as follows: “Every human individual during fetal life normally passes through a period characterized by the presence of numerous cystic renal tubules. Such a normal physiological event, however, may be converted into an abnormal or pathological condition if such tubules do not give way at the end of their allotted time, but continue to grow and expand to the detriment of adjacent structures.” He goes on to 230 GEORGE MORRIS PIERSOL

show how isolated renal cysts can easily result from the persistence and expansion of cystic tubules which fail to collapse, and finally points out that congenital cystic kidneys, where the entire organ is affected, may have their inception in the widespread persistence and cystic degeneration of the cystic uriniferous tubules which he has described.

BIBLIOGRAPHY.

. NAUMANN. Inaug. Dis. Kiel, 1887.

. Bucpee & WotstEIn. Jour. A. M. A. 1924, Vol. XXXIII, P. 1887.

. Atonna & MorrisEy. Annals of Surgery, Vol. 84, P. 846. Dec. 26, 1926. Crawrorp. Surg. Gyneo. & Obstet/Vol. 26/Feb/1923/P. 185.

SIEBER. Deutsche Ztschr. f. Clin. 1905. Vol. 79. P. 469.

. ATONNA & Morrisey. Loc. cit.

. Rovsinc. Am. Jour. Urol. 1912, VIII, 120.

. Kampmeter. Surg. Gyneco. & Obstet. 1923. Vol. 36, P. 208.

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DISCUSSION.

Dr. J. N. Hatt, Denver: I don’t think sufficient emphasis has been laid upon finding the cysts. We have had two cases in the hospital in which the cystic kidney was of importance. In one the man got to a place where there was the ditferential diagnosis to be done on account of his continuous fever. We opened the abdomen to try to find if the right kidney could be taken out and leave the other kidney with enough function to take care of the man’s life. The liver was cystic We removed one kidney, and the man lived for years, but died of failing kidney function.

In another case they operated and found a polycystic kidney and also a polycystic liver.

I think we ought to bear in mind that there are many cases where the liver is involved. I think we ought to bear in mind that when cysts are found in the liver to explore the kidneys, and see what can be done.

Dr. THomas P. Sprunt, Baltimore: There is one interesting feature I would like to ask Dr. Piersol about; it may not be a general feature, but we have been impressed with the fact that these patients show very marked impairment of their renal function and yet clinically they get along fairly well for long periods. I recall one case at Baltimore that was under observation for two years after his phthaléin test was zero. Ordinarily when we get a case of nephritis where there is no phthalein excretion we think death is imminent, but this man lived for two years in fairly good health before he died and came to autopsy. Then there is the case of a woman in the fifties whom we have observed occasionally for the past six years. She has always shown bilateral POLYCYSTIC DISEASE OF THE KIDNEY 231

renal tumors, arterial hypertension and signs of renal insufficiency with a phthalein of 20 per cent., and a high blood nitrogen. She lives in fairly good health, and has no marked symptoms, leading a quiet life.

I wonder how frequent this is in polycystic disease of the kidneys, and how it can be explained. There must be a very gradual loss of renal tissue with loss of function.