Emphysematous pyelonephritis

Emphysematous Pyelonephritis A Repot-tof Two Cases

ALAN M. SPAGNOLA,

M.D.*

Phoenix, Arizona

From the Department of Medrcine, Phoentx lndran Medical Center, Phoenix, Arizona and, The Department of Medicine, Veterans Admintstratron Hospital Syracuse, New York The opinrons expressed In this paper are those of the author and do not necessarily reflect views of the Indian Health Service Requests for reprints should be addressed to Dr Alan M. Spagnola. Manuscript accepted June 10, 1977 Present address: Department of Internal Medicine, Division of Rheumatology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 065 10 l

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Emphysematous pyeionephritis is a suppurative infection of the renal parenchyma characterized by the production of gas by bacteria through fermentation. Although seemingly rare, this condition occurred in two diabetic patients on general medical wards over a two year period. Diagnosis, in an appropriate clinical setting, is confirmed roentgenoiogicaiiy. Escherichia coii is the most common etioiogic organism. Despite appropriate medical and surgical intervention, this severe form of renal parenchymai infection carries a high mortality. The increased risk of infectious complications associated with diabetes mellitus is well known. Certain specific infections among diabetic patients, although well described in the surgical subspeciality journals, are only recently being reported in the general medical and medical subspeciality literature. Examples of such infections include malignant external otitis [l] (a severe infection of the external ear and surrounding structures caused by the organism Pseudomonas aeruginosa) and necrotizing fasciitis [2] (an infection of superficial fascia with extensive necrosis and widespread undermining of surrounding tissues most commonly caused by hemoiytic streptococci and staphylococci). Emphysematous pyelonephritis is another severe infection associated with diabetes meilitus [3-8,141. It is characterized by suppurative infection in the renal parenchyma with the production of intrarenal and occasionally perirenai gas. Twenty-nine cases have been reported to date [3--181. Although not exclusively associated with the diabetic state, the disease carries a more ominous prognosis when found in a patient with diabetes meliitus. Since the prime medical providers for patients with diabetes mellitus are family practitioners and internists, it is important that they become more familiar with these specific infectious complications. in this paper I describe two cases of emphysematous pyelonephrrtis in diabetic patients seen on general medical wards within a two year period and review the pertinent literature regarding this conditron CASE

REPORTS

A 63 year old man was admitted to the Veterans Adminrstration hosprtal for confusron and fever. He was a diabetic of long standing treated wtth oral agents and diet with poor control. He was in good health until two weeks prior to admission when he noted the onset of fatigue, fever with temperature to 102’F, myalgia and generalized abdominal pain Polyuria and nocturia became prominent, and three days prior to admission, generalized progressive weakness and confusion prompted hrm to seek medical attention He denied

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Figure 1. Case 1. Abdominal x-ray film from patient demonstrating emphysernatous pyeionephritis of the righf kidney. The right kidney is outlined by mottled confluent lucenties.

dysuria, pneumaturia, hematuria, previous instrumentation of the urinary tract, or passage of tissue or stones. His past history was pertinent in that he had a right total hip replacement three years prior to admission for degenerative joint disease. He had ingested excessive amounts of alcohol for many years. Physical examination revealed a confused and dehydrated elderly man in moderate respiratory distress. Oral temperature was 103.6*F, pulse rate 120/min, blood pressure 96162 mm Hg and respirations 33/min, Kussmaul in type. The neck was supple. The findings on pulmonary and cardiovascular examination were unremarkable. The abdomen was distended with a prominent venous pattern and shifting dullness. The liver and spleen could not be felt. Moderate suprapubic tenderness and right costovertebral angle tenderness were present. The remainder of the physical examination was within normal limits. Laboratory values on admission included a hematocrit value of 30 per cent, a leucocyte count of 15,600/mm3 with 87 per cent segmented neutrophils, a blood urea nitrogen of 34 mgllO0 ml and a creatinine level of 1.6 mg/ 100 ml. The urine was cloudy with numerous white blood cells/hpf, 4+ glucose and 4-t ketones. Many gram-negative rods were seen on gram stain of the urine. Plasma glucose was 442 mg/lOO ml. Serum sodium was 131 meq/liter, potassium 2.9 meq/liter, chloride 95 meq/liter and carbon dioxide 9 meq/ liter. Serum acetone was positive in a 1:8 dilution. Arterial blood with the patient breathing ambient air revealed a pH of 7.15, a carbon dioxide tension (pCOp) of 15 mm Hg, an oxygen tension (PO,) of 88 mm Hg. Lumbar puncture was within normal limits. Subsequent blood and urine cultures grew Klebsiella. A plain abdominal x-ray film (Figure 1) showed the

F&n? 2. Case 1. Excretory urogram from patient exhibiting normal function of the left kidney and absent function on the right.

right kidney outlined with gas with additional mottled confluent lucencies in the renal parenchyma. Appropriate therapy for diabetic ketoacidosis was initiated with intravenous fluids, potassium replacement and insulin. For the sepsis the patient was initially treated with cephalothin and gentamicin; this was later changed to chloramphenicol when the organism was found resistant to gentamicin. Surgical consultation was obtained. Initial response was favorable with improved mentation and control of sepsis. An excretory urogram on the fifth hospital day (Figure 2) showed no function of the right kidney but normal function of the left. The gas lucencies in the right kidney remained unchanged. On the sixth hospital day the patient underwent total right nephrectomy. The right kidney was totally destroyed by the purulent necrotic process. Microscopic examination of the kidney removed at surgery revealed multiple abscesses throughout with numerous bacteria. Despite initial postoperative improvement, the patient died seven days postoperatively. Permission for postmortem examination was refused. Case 2. A 40 year old Apache Indian woman was admitted to the Phoenix Indian Medical Center with a three week history of dysuria, fever and chills. Two days prior to admission she experienced nausea, vomiting, left costovertebral angle pain and watery diarrhea. She noticed decreasing urinary output for two days prior to admission. One day before admission she experienced dyspnea on exertion. She denied hematuria, passage of tissue or stones, or pneumaturia. There was no

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Figure 4. Case 2. Gross pathologic specimen of &%dney and perirenal bed. The right kidney has been cut in half. The len kidney is totally destroyed, and there is extensive perirenal inflammatory reaction.

Flgure 3. Case 2. Abdominal x-ray ,film from patient showing the left kidney with mottled lucencies throughout. In addition, small perinephric gas cot/e&ions are seen.

history of stricture or previous urinary tract instrumentation. The patient had consumed approximately 2 quarts of wine per day for many years. Eighteen months prior to admission she had acute pyelonephritis, organism(s) unknown, and responded to intravenous antibiotic therapy. Her hyperglycemia was poorly controlled, probably because of her poor compliance in taking insulin or oral hypoglycemia agents. Physical examination on admission revealed an obese woman in acute distress. The oral temperature was 101.6’F, pulse rate 127/min, blood pressure 119/82 mm Hg and respiratory rate 36/min with Kussmaul breathing. There was no diabetic retinopathy and no jugular venous distention. Bilateral rales extended one-third up the posterior portion of the chest. A ventricular gallop was audible without murmers or rubs. The abdomen showed bilateral lower quadrant tenderness without rebound. Bowel sounds were slightly diminished. There was no hepatosplenomegaly. Bilateral costovertebral angle tenderness was elicited, more marked on the left. On admission, the hemocrit value was 36 per cent, leukocyte count 32,600/mm3 with a marked shift to the left, and blood urea nitrogen 32 mg/lOO ml. The urine was cloudy with a 4i- protein, 4-F glucose and negative ketones; mi-

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croscopic examination revealed 20 to 30 white blood cells hpf, 50 to 75 red blood cells hpf and numerous gram-negative rods on smear. Cultures of urine and blood grew out Escherichia coli sensitive to cephalothin, gentamicin and chloramphenicol. Serum sodium was 139 meq/liter, potassium 2.8 meq/liter, chloride 78 meq/liter and carbon dioxide 13 meq/liter. Plasma glucose was 496 mg/ 100 ml. Arterial blood with the patient breathing 4 liters of nasal oxygen revealed apHof7.31,apCOpof 15mmHgandapOpof 120mmHg. Prothrombin time was 15 seconds with a control of 11.3 seconds; partial thromboplastin time of 36 seconds with a control of 18 seconds; platelet count 70,000/mm3, fibrin split products positive >40 ug/ml, serum glutamic oxaloacetic transaminase 229 IU; lactic dehydrogenase 1,033 IU; alkaline phosphatase 65 IU and total bilirubin 2.4 mg/lOO ml. No serum ketones were detected. An x-ray examination of the chest revealed cardiomegaly without infiltrates. A plain abdominal film (Figure 3) showed mottled lucencies overlying the left kidney with small perinephric gas collections. A central venous pressure catheter measured 18 cm H20. The administration of intravenous cephalothin and gentamicin was begun. The patient remained oliguric despite receiving diuretics. The surgical consultant considered operative intervention contraindicated because of the severe sepsis and laboratory evidence of disseminated intravascular coagulation. Persistent metabolic acidosis remained unresponsive to bicarbonate therapy. Hypotension was refractory to the administration of intravenous vasopressors. Severe delirium tremens developed, and she died 36 hours after admission. Postmortem examination showed edema and congestion of the lungs and marked fatty infiltration of the liver. In the left perirenal area there was extensive inflammatory reaction. Upon opening the perirenal fascia, a hissing sound of escaping gas was heard. Grossly, the left kidney (Figure 4) showed complete destruction with loss of all recognizable structures; the right kidney appeared grossly normal. Microscopic examination of the left kidney revealed a

EMPHYSEMATOUS PYELONEPHRITIS-SPAGNOLA

TABLE I

Fatalfty Rates of Surgical Versus Medical Therapy in Emphysematous Pyelonephritls

TotalNo. Cf Patients 31

No. wlth Diabetes

Left

Skie Rfghl

Both

31 (100)

14

15

2

SlUfjiCCl 24

Treatment (died) Medfcal S (33)

7

WC4 5 (71)

NOTE. Numbers in parentheses denote percentages

massive multiple

inflammatory microscopic

polymorphonuclear abscesses.

Numerous

infiltrate

with

bacteria were

seen. The right kidney had changes of diffuse diabetic nephrosclerosis

and acute tubular necrosis without involvement

by the bacterial process.

COMMENT The first reported case of emphysematous pyelonephritis was in 1898 by Kelly and MacCallum [3]. Thirty-one cases have been reported. The two case reports here parallel the clinical presentation of patients described in the literature. Patients with this disease are usually diabetic and critically ill with evidence of sepsis, although indolent infection may precede the acute illness by at least two months [ 41. The disease should be suspected in any diabetic patient with evidence of acute or chronic pyelonephritis. in nondiabetic patients, the presence of gas in the upper urinary tract strongly implies urinary tract obstruction by calculi, neoplasm or stricture [ 51 Both diabetes and obstruction may, of course, occur in the same patient. The history provides few clues that aid in diagnosis. Lower urinary tract symptoms are unusual, and pneumaturia is distinctly uncommon [4,5]. Nausea, vomiting and diarrhea occur in a high proportion of patients [6]. Abdominal pain, usually generalized, may be present. Costovertebral angle tenderness is usually elicited on the involved side. A palpable mass may be felt in the abdomen or flank, as may crepitus when the infection extends outside the perirenal space [7]. Laboratory values are not specific. The leukocyte count is increased in the majority of cases as is the blood urea nitrogen indicating either prerenal factors or superimposed renal disease. In Case 2 of this report the patient had laboratory evidence of disseminated intravascular coagulation. An x-ray examination of the abdomen usually establishes the diagnosis. Mottled lucencies are seen throughout the involved kidney and, possibly, the ureter and bladder. Gas may also be seen surrounding the involved kidney, indicating combined renal and perinephric abscess [ 81. In Case 1 of this report the patient showed combined emphysematous pyelonephritis and emphysematous cystitis, an entity reported only one other time [9]. Emphysematous cystitis is characterized by gas within the wall of the urinary bladder. It occurs in diabetic patients or in patients with bladder neck

obstruction. This entity is more benign than emphysematous pyelonephritis and responds to drainage and antibiotics [4,10,1 l]. In the literature, confusion exists about the best management for patients with emphysematous pyelonephritis. Schultz and Klorfein [ 121, in 1962, and Stokes [ 131, in 1966, reviewed published reports and suggested that surgically treated patients had a poor outcome because the process was often bilateral; therefore, they advocated medical management. In 1968, Schainuck et al. [4] pointed out that, since most gas in bodily tissues readily diffuses into the bloodstream, the continuing presence of gas, despite appropriate medical management, is evidence that the etiologic bacteria are still viable and producing gas through fermentation of glucose. They advocated total nephrectomy if adequate antimicrobial therapy does not result in prompt disappearance of gas by x-ray studies and rapid clinical improvement. Truman and Rutherford [8], in 1971, classified the conditions associated with gas in the urinary tract and helped to allay the confusion in terminology that has existed in the literature. They divided these conditions into gas in the urinary bladder (emphysematous cystitis), ureter (emphysematous ureteritis), renal pelvis (emphysematous pyelitis) and renal parenchyma (emphysematous pyelonephritis). Review of the x-ray studies of 27 cases reported as emphysematous pyelonephritis reveals that only 20 meet the roentgenologic criterion of gas in the renal parenchyma [8]. In seven cases previously described as emphysematous pyelonephritis, gas was actually present in the collecting system alone (emphysematous pyelitis). Six of these seven patients lived. The mortality rate in the 20 true cases of emphysematous pyelonephritis was 50 per cent. Of the 15 patients treated surgically, six (40 per cent) died, and, of the five patients treated medically, four (80 per cent) died. These workers stressed the high fatality rate associated with this disease and showed that the mortality rises sharply as gas forming infections extend from collecting system to renal parenchyma and, finally, to the perinephric space. Table I shows the fatality rates of medical versus surgical therapy in the 31 cases of true emphysematous pyelonephritis reported in the literature. Over-all mortality is 42 per cent. Of the seven patients treated medically, five died (70 per cent). Of the 24 patients treated surgically, eight died (33 per cent). The decline

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in over all mortality rate in recent years is attributable to earlier aggressive surgical intervention. The diagnosis of this disease ‘is confirmed by the roentgenologic detection of gas within the renal parenchyma. Although usually readily apparent, the gas may be obscured by overlying bowel gas, causing a delay in diagnosis [6,15]. Aerobic gram-negative rods predominate as the causative organisms in this severe necrotizing infection. Esch. coli is the organism most commonly isolated (50 per cent), but other gram-negative organisms have also been cultured, such as Proteus, Pseudomonas, Aerobacter and Klebsiella [ 51. Clostridia, despite its propensity for gas production in other bodily tissues, has never been isolated as the causative organism in emphysematous pyelonephritis

[41. The etiology of emphysematous pyelonephritis remains obscure. It has been postulated that the high glucose concentration in the tissue of patients with diabetes mellitus provides the substrate for organisms which are able to produce carbon dioxide and hydrogen by the fermentation of sugar [ 12,131. This explanation does not explain the rarity of this disease despite the high incidence of coliform urinary tract infection in diabetic patients. Another theory emphasizes that two features uniformly found in emphysematous pyelonephritis are severe necrotizing infection and impaired tissue and vascular response, caused by local factors, such as obstruction, and systemic factors, such as diabetes mellitus. This impaired host response may enable organisms capable of producing carbon dioxide to utilize necrotic tissue as a substrate to generate gas In diabetic patients with evidence of pyelonephritis and abdominal pain, crepitus or flank mass, or in diabetic patients not responding to the usual measures for

urinary tract infection, an abdominal x-ray study should be obtained. If this film reveals gas in the renal parenchyma or perinephric space, a retrograde pyelogram should be performed to search for obstruction [ 141. An excretory urogram will usually show a nonfunctioning kidney on the involved side but may give some indication of the remaining renal function. If there is evidence of obstruction (stricture, stone, neoplasm), appropriate surgical intervention is indicated. If no obstruction is present, a brief trial of high dose antibiotic therapy against gram-negative organisms, especially Esch. coli, is warranted. Chloramphenicol has been useful as an initial antibiotic until definitive culture and sensitivity results are available. If toxic symptoms continue, clinical deterioration occurs, or renal or perirenal gas collections persist on roentgenograms despite appropriate antibiotic therapy, total nephrectomy should be the treatment of choice [ 141. Although only two cases of bilateral disease have been reported [9,18], another patient has been described who had a nephrectomy for emphysematous pyelonephritis and who later had a similar infection in the remaining kidney [ 191; therefore, life-long antibacterial prophylaxis is recommended after nephrectomy for this disease [ 141. Incision and drainage are recommended for patients who will not tolerate nephrectomy [ 141. With early surgical intervention the survival rate is improving, but, even with early surgical therapy, the mortaltty approaches 33 per cent. As shown from the gross pathologic specimen of the patient (Case 2) In thts report, antibiotic therapy alone without surgical drainage in such a severe destructive process is hopeless. If the emphysematous process involves both kidneys, nothing short of bilateral nephrectomy with maintenance dialysis appears warranted

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Caky DA, Bentley DW, Lowy K, et al : Malignantexternalotttis, A severe form of otitis tn dtabeticpatients Am J Med 61. 298,302, 1976 Rea WI, Wyrick WJ: Necrotizlng fasclitts Ann Surg 172 957, 1970. Kelly HA, MacCallum WG: Pneumaturta JAMA 31 375, 1898. Schainuck LI, Fouty R Cutler RE Emphysematous pyelonephritis. Am J Med 44. 134, 1968 Costas S. Renal and perirenal emphysema Br J Urol44: 3 11, 1972. Ireland GW, Javadpour N, Case AS Renal emphysema and retention of renal fun&on. J Urol 106: 463, 1971 Clifford NJ, Katz I. Subcutaneous emphysema compllcatmg renal infection by gas forming coliform bacteria. N Engl J Med 266: 437, 1962. Turman AE, Rutherford C: Emphysematous pyelonephntis with perinephric gas. J Urol 105: 165, 1971 Harrison JH, Bailey OT: Significance of necrotizing pyelonephritis in diabetes mellitus. JAMA 118. 15, 1942 Lee JB: Cystitis emphysematosa Arch Intern Med 105. 150,

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1960 Milner WA, Garlick WB, Mamonas C Cystitis emphysematosa, case report wtth clinical dtagnosis and review of the literature. N Engl J Med 246: 902, 1952 Schultz EH, Klorfein EH. Emphysematous pyelonephrltls J Urol 87. 762, 1962. Stokes JB: Emphysematous pyelonephritls J Urol 96 6, 1966 Dunn SR, DeWolf WC, Gonzales R Emphysematous pyelonephritis J Urol 114: 348, 1975. Klein DE, Mahoney SA, Youngen R, et al . Renal emphysema. J Urol 95: 625, 1966 Rosenberg JW, Quader A, Brown JS: Renal emphysema Urology 1. 237, 1973 Bliznak J, Ramsey J: Emphysematous pyelonephritls Clin Radio1 23. 61, 1972. Gillies CC, Flocks R: Spontaneous renal and perlrenal emphysema. Report of a case in a diabetic from escherichla co11infection Am J Roentgen01 46: 173, 1941 Davies CJ, Smtth PJ. Renal emphysema; short case report Br J Urol 46: 107, 1974.