Focal Pyelonephritis: A Cause of Severe Hematuria1

THE JOURNAL OF UROLOGY

Vol. 64, Ko. 3, September 1950 Printed in U.S.A.

FOCAL PYELONEPHRITIS: A CAUSE OF SEVERE HEMATURIA1 HARRISON C. HARLIN Department of Urology

LEEN. FOSTER Department of Pathology Lawson V. A. Hospital, Chamblee, Ga. AND

C. P. ARMSTRONG

At the eighth annual meeting of the American Urological Association in 1909, Dr. Granville MacGowan of Los Angeles presented a paper entitled "Persistent Hematuria Arising From Angioma of Papillae of the Kidney." Three cases of this condition treated by the 'conservative operation' of nephrotomy (pole to pole exposure, laying open all of the calyces) and papillectomy were reported. Reference to Harry Fenwick's report of 6 analogous cases in 1903 and Cabot's case in 1909 was made. One of the discussors of this presentation was Dr. Hugh Cabot who made the following statement: "I think the pathological condition is still obscure." Despite the advances in urology, improved x-ray techniques, and closer clinicalpathologic correlations, the true nature of many of these lesions is still not fully understood. It is certain, however, that the knowledge of the existence of such a condition, whatever the etiology may be, has resulted in a lessening of the loose use of the terms 'essential hematuria' and 'idiopathic hematuria' in the literature. Kretschmer believes that these terms should disappear completely; A. R. Stevens has made the plea "to content one's self with an anatomic diagnosis only." McKay, along with Kretschmer, believes as do we, that any kidney that bleeds will reveal some pathological condition if examined properly. Through the years excellent discussions and case presentations have been added to the literature and thereby have done their part to raise the curtain on "hematuria, cause undetermined." It is not our purpose here to present a detailed review of the subject, this having been admirably done by Riley and Swann in 1941 and by McKay, Baird and Lynch recently. Suffice it to say that to date approximately 75 cases of severe hematuria have been reported under the diagnosis of renal varix or angioma of the kidney, and another group of less than 25 under diagnoses referable to inflammatory changes in the renal papillae. vVe present here an additional 2 cases of severe recurring hematuria necessitating nephrectomy, in which the anatomic change seemed to cause them to fall into the infectious group. The second case was diagnosed correctly preoperatively, the first was not. 1 Published with permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or the conclusions drawn by the authors. 445

446

HARRISON C. HARLIN, LEE N. FOSTER AND C. P. ARMSTRONG CASE REPORTS

Case 1. M. E. C. (RNo. 6990 L. V. A.H.), a47 year old whitefarmer, was admitted to the hospital on October 16, 1947, complaining of hematuria. The patient stated that 5 days before admission he experienced asymptomatic hematuria -the blood being present throughout the act of urination. This had continued until admission time. There was a past history of hematuria associated with mild right flank pain in 1942. The diagnosis of "nephritis" was made at that time. No interim history of hematuria, flank pain, dysuria, etc., was obtained. Family history and further past history were noncontributory. Physical examination revealed a well developed, well nourished white man in no acute distress. The blood pressure was 118/78. No abnormalities were noted. Laboratory studies revealed a hemoglobin of 86 per cent. The white blood count was 6,000 with 45 per cent lymphocytes. The bleeding time, coagulation time and platelet count were normal. The urine was loaded with red blood cells and

FIG. 1. Parenchymal pressure causing defect and incomplete filling of calyx as shown by urography.

contained 4 plus albumin. The nonprotein nitrogen was 38 mg. per cent and total protein was 7 gm. The Kahn test was negative. Urine obtained from both kidneys by ureteral catheter resulted in sterile cultures. Bladder urine grew hemolytic staphylococcus and nonhemolytic streptococcus. Smears and cultures for tubercle bacilli were repeatedly negative. Cystoscopy performed soon after admission revealed the presence of a few dark old blood clots in the bladder. There was a diffuse mild inflammatory reaction of the bladder mucosa but no bleeding point was noted. No blood came from either ureteral orifice and clear urine was obtained bilaterally by means of catheterization. The patient continued to experience intermittent hematuria and on one occasion gross blood was seen spurting from the right ureteral orifice. Urograms revealed a persistent deformity of the right upper calyx (fig. 1). The left kidney was normal in appearance and function.

FOCAL PYELONEPHRI'l'IS: CAUSE OF SEVERE HEMATURIA

447

Since the bleeding continued unabated the patient was taken to the operating room on October 12, 1947, with the preoperative diagnosis of tumor of the right kidney, and a right nephrectomy was performed. The kidney appeared normal externally. The gross specimen was a kidney measuring 10.5 by 6.8 by 3.2 cm. It weighed 139.5 gm. A moderate amount of perirenal fat covered the external surface; the capsule stripped with slightly increased difficulty. The cut surface of the cortex and medulla were greyish-tan, and the glomeruli of the cortex were made out with difficulty. Tubular striations in some pyramids were absent while in others,

FIG. 2. Demonstration of irregular cyst-like dilatation in upper pole lined with glistening, hyperemic, mottled, purple fibrotic tissue.

particularly the lower pole, they were prominent. The cortex and medulla were not well demarcated in some regions, but in the lower pole the cortex had an average thickness of 0.8 cm. while the corresponding medulla had an average thickness of 2 cm. In the upper pole there was an irregular, cyst-like dilatation lined with glistening, hyperemic, mottled, purple, fibrotic tissue. The pelvis was not markedly thickened of dilated. Other calyces showed essentially no abnormalities (fig. 2). Sections were taken through the cortex and medulla from two regions and from the cyst-like dilatation mentioned. On microscopic examination (fig. 3, A) the cyst was lined with a singlelaver of imperfectlydemonstratedcuhoidal epithe-

448

HARRISON C. HARLIN, LEE N. FOSTER AND C. P. ARMSTRONG

lium supported by a thick collar of dense fibrous connective tissue. The renal parenchyma surrounding the cyst was heavily infiltrated with lymphocytes and plasma cells, and an intense overgrowth of fibrous tissue had occurred. The glomeruli, for the most part, were hyalinized. Those remaining showed evidences of early scarring. The tubules were dilated and lined with a flattened epithelium. Many contained colloid casts. In some instances the tubular epithelium was proliferated, forming irregular serrated cavities filled with a pink colloid material. The arteriolar intima of all vessels about the cyst was enormously thickened, and the vessel endothelium was prominent. A vascular granulation tissue formed an irregular sheath about the fibrous cyst and extended among the surrounding tubular structures. Many of the tubules contained large golden-brown granules and casts of hemosiderin. Random sections secured at sites remote from the renal cyst showed no unusual changes. Diagnosis: Renal cyst with focal pyelonephritis. The postoperative course was uneventful. No further bleeding has been experienced. Case 2. A. M. (R No. 7740 L. V. A.H.), a 22 year old Negro, was admitted to the hospital on November 29, 1947, with a diagnosis of sickle cell anemia and hematuria. His history dated back to 1945 when, while in the army, he experienced hematuria for the first time. This was followed by frequent passage of dark clots and bright red blood for a period of 7 months. Spontaneous cessation of bleeding then occurred. He was hospitalized for 13 months from the onset of hematuria, at the end of which time he was discharged with a diagnosis of tlickle cell anemia. The patient then remained asymptomatic until 3 weeks before his admission to this hospital when he noted hematuria which lasted 2 or 3 days. Approximately 8 days before admission severe hematuria was experienced with passage of a large quantity of red blood and a few dark clots. This condition persisted until admission. The past history, except that mentioned, was noncontributory; there was no familial history of blood dyscrasia, carcinoma, or tuberculosis. There was no history of ulceration of the skin of the lower extremity. The blood pressure was 100/70. The only abnormal physical findings were a palpable spleen, 2 cm. below the costal margin, and a soft systolic murmur heard at the apex and mitral area. The mucous membranes were generally pale. Laboratory studies showed a red blood cell count of 1,800,000 with hemoglobin 30 per cent of normal. The urine was grossly bloody, the pH 7, the specific gravity 1.012, sugar negative, albumin 4 plus, the microscopic examination revealed only blood. A urine culture was negative and three consecutive 24 hour urine specimens showed no acid fast bacilli. Subsequent reports of cultures and guinea pig inoculations bore this out. The blood Kahn test was negative. The platelet count was 500,000, bleeding time 1 minute, coagulation time 5 minutes. On cystoscopy the bladder was found filled with blood clots. After evacuation of clots the bladder was seen to be essentially normal except for gross blood spurting from the right ureteral orifice. Catheters were passed bilaterally to 27 cm. without obstruction. Retrograde pyelograms were normal except for what appeared to be an incomplete filling of a middle minor calyx of the upper calyceal group (fig. 4). Repeated cystoscopies and urograms revealed similar findings.

FOCAL PYELONEPHRITIS: CAUSE OF SEVERE HEMATURIA

449

On December 4 a sickling preparation showed 5 per cent of all red cells sickling. By December 17 the bleeding had slowed down and from then on was only intermittent. By means of repeated blood transfusions, total of 8000 cc of whole

Fm. 3. A, cyst wall is fibrous. Renal parenchyma forming wall is heavily infiltrated with inflammatory cells. B, note accumulation of fibrous tissue in apex of renal pyramid. A large blood filled sinusoid is present.

Fm. 4. Parenchymal changes resulting in narrowing of entire involved calyx, infundibulum included.

blood, the blood picture became normal. On January 27 no sickling of the red blood cells was observed at the end of 24 hours in all oxygen free preparations. In spite of a normal blood picture the patient continued to bleed, and on February 4, 1948 the patient was taken to the operating room with the diagnosis of renal

450

HARRISON C. HARLIN, LEE N. FOSTER AND C. P. ARMSTRONG

varix or focal pyelonephritis. A nephrectomy (H.C.H.) was performed. There was no evidence of perirenal infection, old or recent. The blood supply to the organ was not anomalous. The kidney when removed was normal in appearance. The gross specimen was a kidney that measured 10.5 by 6.5 by 3 cm. The surface was smooth, the capsule thin. The capsule stripped with ease and left a finely granular surface. The cut surface revealed the cortex to measure 6 mm., the medulla 15 mm. The pelvis was smooth. The calyces followed a normal distribution. The superior middle calyx contained an 0.2 by 0.3 by 1 cm. clot. There was a small 2 mm. submucosal hemorrhagic area in the proximal edge of this calyx. Microscopic study of a section taken through the pyramid and cortex supplying the involved calyx revealed a striking accumulation of dense hyalin collagen about the collecting tubules in the tip of the pyramid (fig. 3, B and fig. 5). Collagen masses extended outward along the tubular structures, becoming less pro-

Fm. 5. Case 2. Section of renal cortex showing scarring of interstitial tissue and glomerular tuft, lymphocyte infiltration, proliferation of remaining tubular epithelium, and colloid casts.

nounced as they approached the cortex. Occasional focal aggregates of fibroblasts were seen surrounding degenerating tubular structures. The epithelium covering the tip of the papilla was thickened in part, and in some places became atrophic being only one cell thick. In the thickened areas, the epithelial cells contained rounded eosinophilic inclusions within their cytoplasm. A small amount of clotted blood was adherent to the mucosal surface. In the cortical portion of the kidney supplying this papilla, there was a diffuse increase in the connective tissue stroma. This was especially well seen about the glomerular capsules. Most of the glomeruli were well demonstrated, although some were hyalinized completely, and occasional instances of partial glomerular sclerosis were seen. The epithelium of many of the tubules was atrophic and flattened and their lumens were filled with a homogenous eosinophilic hyaline material. Focal collections of lymphocytes appeared scattered through the cortical stroma. Diagnosis: Interstitial nephritis with severe sclerosing papillitis.

FOCAL PYELONEPHRITIS: CAUSE OF SEVERE HEMATURIA

451

Postoperative course was uneventful and no further bleeding has been experienced. DISCUSSION

The mechanism of development of hemorrhage in these 2 patients is unexplained. The striking hemorrhagic phenomena are in contrast to the clinical symptoms usually seen in necrotizing papillitis or other forms of pyelonephritis (Kretschmer). Focal chronic pyelonephritis was present in both instances, being anatomically associated with the calyx from which hemorrhage occurred. In the first case the involved renal parenchyma formed a thin shell about the cyst suggesting the disturbed relationships caused by the cyst had induced the inflammatory change. Homosiderin and products of red cell breakdown were present in many tubules in the area of involvement but no evidence of blood within tubules could be demonstrated. No red cell casts -were present in the second case but large blood sinuses were noted in the tip of the involved renal pyramid. These had developed in a bulky hyalin fibrous tissue most prominent in the apex of the papilla. In view of the absence of blood in the proximal tubules it would seem probable that bleeding in each instance would result from rupture of small capillaries or sinuses in the pyramid with extravasation into collecting tubules or escape of blood directly through pelvic mucosa rather than through the upper nephron unit. Clinically, the urograms in the first case revealed a calyceal defect caused by alterations in the adjacent renal parenchyma. In this particular instance ,ve could not be sure preoperatively that a neoplasm was not present and it was for this reason that nephrectomy was performed. The bleeding here, although troublesome, might otherwise not have necessitated resection. The second case presented a some,vhat different problem.The urograms revealed a narrowing of the involved minor calyx, infundibular portion included. Preoperatively the diagnosis of focal pyelonephritis was made. Nephrectomy was necessary because the bleeding was severe, recurrent and uncontrollable. In these instances the urine cultures from the affected kidneys were negative. Quinby, McKay et al. and MacGowan also reported similar cases with negative urine cultures. On the other hand, Braasch, discussing Spitzer's paper, mentioned 'several' cases in which the urine contained a varying number of pus cells and often colon bacilli. Hematuria and albuminuria were constant findings in the active phases of the disease. Pain and other constitutional symptoms are variable and present no definite pattern. In general the following would seem true. U rograms in many instances will show no abnormalities. Progression of the disease with recurrent hemorrhage and scarring may result in narrowing of the infundibular portions of a calyx or of the entire calyx, fuzziness of the calyceal borders or actual pressure defects. The patient -will usually give a history of repeated bouts of bleeding, some over a period of several years. Varying diagnoses, the most common being nephritis (Bright's disease) »·ill have been given. Differential diagnosis must include the various blood dyscrasias, renal tuberculosis and renal neoplasm. Urographic evidence of filling defects resulting from blood clots retained in the kidney pelvis or calyceal

452

HARRISON C. HARLIN, LEE N. FOSTER AND C. P. ARMSTRONG

system must not lead to the erroneous diagnosis of papillary tumor of the renal pelvis. Many of the milder cases may be followed over an indefinite period of time with the aid of a general supportive therapy including hematemics, vitamins and a nourishing diet. Regular check urograms should be done. So long as the patient's general welfare is not impaired and so long as there is no suspicion of other disease (malignancy, tuberculosis) in the kidney, there is no need for operative intervention. In any case, however, where hematuria is persistent, unilateral, severe and debilitating, and the other kidney is adequate, nephrectomy should be performed. In the presence of contralateral kidney disease, conservation of kidney tissue must not be forgotten. SUMMARY

Two cases of severe recurring hematuria necessitating nephrectomy are presented. In these the striking morphologic change is chronic focal pyelonephritis and papillitis. Clinically renal bleeding is the salient feature while associated urographic findings may range from normal to slight defects caused by renal parenchymal change.

424 Vision St., Brooklyn 35, N. Y. (H. C. H.) REFERENCES BRAASCH, W. F.: In discussion of Spitzer's paper, J. A. M.A., 63: 2110, 1914. CABOT, H.: Am. J. Med. Sc., 137: 98, 1909. FENWICK, H.: Clinical Cystoscopy. London, 1904. KRETSCHMER, H.: J. A. M.A., 61: 17, 1913. KRETSCHMER, H.: In discussion of Spitzer's paper, J. A. M.A., 63: 2110, 1914. MACGOWAN, G.: Trans. Am. Urol. Assoc., 3: 238, 1909. MAcGowAN, G.: J. Urol., 9: 331, 1923. MACKEY, W. A.: Brit. J. Surg., 18: 308, 1930. McKAY, H., ET AL.: J. Urol., 61: 1, 1949. McLEAN, E. AND MATHEWS, T. J. AND WEST, J.: Surg., 50: 47, 1942. PILCHER, P.: Ann. Surg., 49: 652, 1909. PILCHER, P. M.: Trans. Am. Urol. Assoc., 5: 215, 1911. PRIESTLEY, J. T. AND WILBUR, D. J.: Proc. Staff Meet. Mayo Clin., 9: 348, 1934. QUINBY, W. C.: J. Urol., 4: 209 1920. RANDALL, A.: J. A. M.A., 60: 10, 1913. RILEY, A. AND SWANN, W.: Urol. & Cutan. Rev., 45: 377, 1941. ROBBINS, S. L., MALLARY, G. K. AND KINNEY, T. D.: New Eng. J. Med., 235: 885, 1946. ROTTINO, A. AND MAHAN, H.: J. Urol., 51: 601, 1944. SPITZER, w.: J. A. M.A., 63: 2110, 1914. STEVENS, A. R.: J. A. M.A., 79: 1302, 1922. YouNG, E.: Surg., Gynec. & Obst., 31: 478, 192).