VIGNETTE IN CLINICAL PATHOPHYSIOLOGY
Surgery in the Management of Autosomal Dominant Polycystic Kidney Disease Lawrence W. Elzinga, MD, John M. Barry, MD, and William M. Bennett, MD INDEX WORDS: Autosomal dominant polycystic kidney disease; cyst marsupialization; abdominal pain; cyst reduction.
R
EFRACTORY abdominal and flank pain often severe enough to require narcotics is present in many patients with autosomal dominant polycystic kidney disease. When conservative measures fail to provide symptomatic relief, the question of referral for cyst reduction surgery can be raised. CASE REPORT A 46-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) was referred to Oregon Health Sciences University because of abdominal distention due to massive bilateral kidney enlargement. ADPKD had been diagnosed by intravenous urography at age 19, during an evaluation for abdominal pain associated with a mass. During the ensuing years, she noted a progressive increase in her abdominal girth, as a result of her enlarging kidneys, and experienced progressive physical discomfort and social embarrassment. She was the subject of jokes at her place of employment about constantly being pregnant because she wore maternity clothes to be comfortable. Multiple physicians had told her that there were no therapeutic options available, except for analgesics and repeatedly advised against cyst aspiration or cyst reduction surgery for fear of impairment of renal function. Four months before referral, serum creatinine was 88.4 mmol/L (I mg!dL) and two 24-hour endogenous creatinine clearances were 1.42 and 1.28 mL/s (85 and 77 mL/min), respectively. Abdominal ultrasound at that time showed large kidneys measuring 21 X II X 18 cm on the right, and 17 X 13 X 19 cm on the left. Both kidneys contained less than 25% normal parenchyma and more than 15 cysts per kidney. The largest single cyst in the right kidney was 12.5 cm, with most of the remaining cysts being larger than 5 cm. In the left kidney, the largest cyst measured 13 cm, with most of the remaining cysts measuring 2 to 5 cm. There were no hepatic cysts noted, and there was no evidence of ascites. On admission to our hospital, she was taking no antihypertensive or analgesic medications. Physical examination showed a well-developed woman whose weight was 62.5 kg. Blood pressure was 130/96 mm Hg. Her abdomen was markedly protuberant, due to large abdominal masses. Her waist was 100 cm in circumference, and her mid-abdominal girth measurement was 114 cm. There was I + pretibial edema bilaterally. Her admission laboratory studies showed a blood urea nitrogen (BUN) of 6.8 mmol/L (19 mg/dL), serum creatinine 79.6 /Lmol/L (0.9 mg/dL), serum albumin 38 g/L (3.8 gfdL); hematocrit 45%; and urinalysis, which showed no protein or casts. There were 4 to 5 white blood cells per high-
power field, but urine culture and sensitivity showed no bacterial growth. A computerized tomography (CT) scan of her abdomen confirmed massively enlarged kidneys bilaterally due to the presence of enormous cysts, occupying most of the abdomen and distorting other intra-abdominal structures. The CT scan confirmed a right kidney greater than 23 cm in length, and a left kidney greater than 24 cm in length. After obtaining informed consent, a bilateral cyst reduction operation was performed through a midline incision extending from the xiphoid process to the pubis. The peritoneal cavity was entered and the right and left colons were reflected medially to expose the kidneys for unroofing of the cysts. Several of the larger cysts were aspirated, including 3,050 mL from a single cyst in the left kidney, as well as 540 mL, 270 mL, 210 mL, and 130 mL from individual cysts in that same kidney. A total of 7,600 mL of cyst fluid was collected from the two kidneys. Superficial cysts were unroofed with electrocautery, and through the cavities of the unroofed cysts, the domes of deeper cysts were also unroofed. Following completion of cyst decompression, bilateral suction drains were placed posterior to the kidneys in the retroperitoneum. During surgery, the patient received I U of autologous whole blood, 2 L of crystalloid solution, and 25 g of mannitol. Estimated blood loss at surgery was 250 mL. At the time of closure, her mid-waist girth was 83.8 cm and her mid-abdominal girth at its greatest point was 90.2 cm. Preoperative and postoperative appearance of the patient's abdomen and her CT scans are shown in Figs I and 2. The patient had a relatively smooth postoperative course. However, she did require 2 to 3 L of crystalloid for the first 2 to 3 days postoperatively to maintain her systolic blood pressure at 110 mm Hg. She was discharged from the hospital on the ninth postoperative day with a BUN of 2.5 mmol/L (7 mg!dL) and a serum creatinine of 70.7 /Lmol/L (0.8 mg! dL). Her discharge weight was 48.9 kg. Follow-up at I month showed an endogenous creatinine clearance of 1.75 mL/s (105 mL/min), a stable blood pressure of 120/82 mm Hg, and complete relief of symptoms of abdominal pain and discomfort. She was active, playing tennis, and without symptoms. She did require repair of an incisional hernia 9 months after surgery. A 3-year follow-up shows continued relief of pain without increase in abdominal girth and normal blood pressure From the Departments of Medicine and Urology, Oregon Health Sciences University, Portland, OR. Address reprint requests to William M. Bennett, MD, L463 Division of Nephrology, Oregon Health Sciences University, Portland, OR 97201. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/1901-0017$3.00;0
American Journal of Kidney Diseases, Vol XIX, No 1 (January), 1992: pp 89-92
89
ELZINGA, BARRY, AND BENNETT
90
but in individual cases, pain can be severe with cysts that are only moderate in size. Mild, nonnarcotic analgesics suffice in most patients. There is a subgroup of APKD patients who develop refractory, disabling pain so severe that they require narcotic analgesics for relief. In such individuals, more radical approaches have been considered. Relief of symptoms by cyst decompression was first reported by Rovsing in 1911. 2 Despite many reports of impressive relief of pain by surgical decompression, emptying of cysts by needle puncture or actual removal of cyst walls, allowing drainage of fluid into the abdomen, was abandoned in the late 1950s, primarily because of the report by Bricker and Patton of two patients who developed decreased glomerular filtration rate with surgical decompression. 3 It was the contention of these investigators that cyst reduction surgery should be abandoned because of the potential loss of functioning cystic nephrons by the surgical procedure itself. It should be noted in
Fig 1. Preoperative (top) and postoperative (bottom) views of the patient's abdomen.
without medications. Serum creatinine was 88.4 ILmol/L (1 mgjdL) at 3 years, with a creatinine clearance of 1.66 mL/s (99.4 mL/min).
Questions I. What is the role of cyst reduction surgery in providing symptomatic relief of pain in patients with ADPKD? 2. What effect does cyst reduction surgery have on renal function in patients with ADPKD?
DISCUSSION
Abdominal pain is a common symptom in patients with autosomal dominant polycystic kidney disease. Usually, the pain is dull and constant, localizing to the flank or lateral abdomen. At times it may be colicky and sharp, and the alert clinician needs to keep in mind that obstruction of the ureter due to a large cyst, blood clot, stone, or neoplasm can produce pain that is superimposed on the chronic pain of patients with polycystic kidney disease. In the classical, longitudinal studies of Dalgaard, pain gradually increasing over a patient's lifetime ultimately affected more than 50% of individuals. 1 Pain, when present, has a general relationship with the size of the kidneys,
Fig 2. CT scans before (top) and after (bottom) cyst reduction surgery.
SURGICAL TREATMENT OF POLYCYSTIC KIDNEYS
reviewing that report that one of the patients actually had a transient improvement in kidney function, and the rate of renal functional decline before surgery was not specified. In 1980, Shangzhi et al reported encouraging long-term pain relief in a group of 52 patients, who had been operated on because of symptomatic polycystic kidney disease. 4 In the Chinese experience, pain relief was striking with no loss of kidney function. We decided to reexamine surgical cyst decompression in a group of patients, such as the present case, who were referred for refractory pain management. 5 Ultrasound-guided percutaneous aspiration of cyst fluid from the largest cysts on the side or sides affected was first accomplished without complications. All patients experienced dramatic pain relief, but in most patients the duration of that relief was transient. The actuarial probability of a patient being pain-free 18 months after cyst aspiration alone was 33% ± 17%. Using the recurrence of pain within 6 months following cyst aspiration as an indication for surgery, we reported that six patients received impressive pain relief" with a probability of a patient being painfree 18 months after surgery of 81 % ± 12%. 5 There was no loss of kidney function after either aspiration or surgery. The question of recurrence of large cysts after surgical decompression has not been addressed in any systematic manner. Some centers instill alcohol as a sclerosing agent to prevent secretion of fluid and reoccurrence of the cysts. This has not been a problem in our clinical experience and the maintenance of pain relief over long periods of time has been excellent, as illustrated by the present case. The question of the effects of surgery on renal function is more difficult to answer. Initially, it was proposed that removal of cysts and cyst fluid would contribute to the overall decline in glomerular filtration rate. However, even on theoretical grounds, the loss of several hundred cystic nephrons should make little difference to whole kidney function, since the adult kidney has approximately 1 million nephrons and only 2% to 10% are cystic. Further, if renal dysfunction is produced by the pressure of cysts on adjacent normal parenchyma, it is possible that reduction of cyst volume might actually result in renal functional improvement. Our case demonstrated a 20% to 25% improvement in kidney function,
91
which has been maintained over 3 years. It is impossible to say whether this was a result of the surgery. Furthermore, in a large experience with surgical reduction of cyst volume in patients from the Mayo Clinic and Oregon Health Sciences University, no change in the slope of the l/creatinine line can be demonstrated as a result of this surgical procedure. 6 This is somewhat different from the more optimistic reports of the Chinese investigators. It is possible that more extensive surgery, with removal of more cysts, would be beneficial, or alternatively, that the cyst surgery has no beneficial effect. Certainly, contrary to the predictions of Bricker and Patton in the 1950s, marked deterioration in renal function, which was the major reason that the surgical procedures were abandoned, has not been experienced. A careful review of the literature on the effects of cyst reduction surgery, showed little adverse and many favorable outcomes on renal function in the period of time between 1911 and 1960. 7 This experience is all the more remarkable because most of the surgery was performed before the availability of routine dialysis and modern antibiotics. Nearly all the fatalities following surgical decompression had advanced preoperative renal failure or postoperative infections. At the present time, improvement of renal function cannot be used as an indication for performing cyst-reduction surgery, based on any data available in the literature. However, in patients with refractory symptoms, one can be relatively confident with an experienced surgical team, that renal functional decline will not result directly due to the surgical procedure. In our hands, the relief of symptoms is impressive. One final benefit of a surgical approach might be amelioration of high blood pressure, which is known to cause acceleration of renal functional decline in polycystic kidney disease. The present patient was mildly hypertensive before surgery and has not required antihypertensive medicine or experienced elevated diastolic blood pressures since the surgical procedure 3 years ago. There is also reported experience in the literature of improvement in blood pressure control with cyst reduction surgery. An extensive review of previous experience with cyst reduction surgery has been published. 7 Thus, it can be concluded from this case that appropriate patients with refractory symptoms may be benefited by a reduction of cyst volume
92
ELZINGA, BARRY, AND BENNETI
by aspiration or surgery. It is our preference to perform cyst aspiration oflarger cysts to give the patient an idea of the type of symptomatic relief that can be expected from more extensive surgery. We then operate on patients in whom symptoms
recur following the aspiration. We occasionally are surprised by patients who obtain prolonged, and in one case permanent, relief of symptoms with a single cyst aspiration under ultrasound guidance.
REFERENCES 1. Dalgaard OZ: Bilateral polycystic disease of the kidneys: A follow-up study of 284 patients and their families. Acta Med Scand 158:1-255, 1957 (suppl 328) 2. Rovsing T: Treatment of multilocular renal cyst with multiple punctures. Hospitaistad 4: 105, 1911 3. Bricker NS, Patton JF: Renal function studies in polycystic disease of the kidney with observations on the effect of surgical decompression. N Eng! J Med 256:212-214, 1957 4. Shangzhi H, Shiyuan A, Henning J, et ai: Cyst decapitating decompression operation in polycystic kidneys. Chinese Med J 93:773-778, 1980
5. Bennett WM, Elzinga L, Golper TA, et al: Reduction of cyst volume for symptomatic management of autosomal dominant polycystic kidney disease. J Urol 137:620-625, 1987 6. Elzinga L, Barry J, Torres V, et al: Cyst decompression surgery for autosomal dominant polycystic kidney disease. Kid Int 37:247, 1990 (abstr) 7. Bennett WM, Elzinga LW, Barry JM: Management of cystic kidney disease, in Gardner KD, Bernstein J (eds): The Cystic Kidney. Dordrecht, Netherlands, Kluwer, \990, pp 247275
Surgery in the Management of Autosomal Dominant Polycystic Kidney Disease Lawrence W. Elzinga, MD, John M. Barry, MD, and William M. Bennett, MD INDEX WORDS: Autosomal dominant polycystic kidney disease; cyst marsupialization; abdominal pain; cyst reduction.
R
EFRACTORY abdominal and flank pain often severe enough to require narcotics is present in many patients with autosomal dominant polycystic kidney disease. When conservative measures fail to provide symptomatic relief, the question of referral for cyst reduction surgery can be raised. CASE REPORT A 46-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) was referred to Oregon Health Sciences University because of abdominal distention due to massive bilateral kidney enlargement. ADPKD had been diagnosed by intravenous urography at age 19, during an evaluation for abdominal pain associated with a mass. During the ensuing years, she noted a progressive increase in her abdominal girth, as a result of her enlarging kidneys, and experienced progressive physical discomfort and social embarrassment. She was the subject of jokes at her place of employment about constantly being pregnant because she wore maternity clothes to be comfortable. Multiple physicians had told her that there were no therapeutic options available, except for analgesics and repeatedly advised against cyst aspiration or cyst reduction surgery for fear of impairment of renal function. Four months before referral, serum creatinine was 88.4 mmol/L (I mg!dL) and two 24-hour endogenous creatinine clearances were 1.42 and 1.28 mL/s (85 and 77 mL/min), respectively. Abdominal ultrasound at that time showed large kidneys measuring 21 X II X 18 cm on the right, and 17 X 13 X 19 cm on the left. Both kidneys contained less than 25% normal parenchyma and more than 15 cysts per kidney. The largest single cyst in the right kidney was 12.5 cm, with most of the remaining cysts being larger than 5 cm. In the left kidney, the largest cyst measured 13 cm, with most of the remaining cysts measuring 2 to 5 cm. There were no hepatic cysts noted, and there was no evidence of ascites. On admission to our hospital, she was taking no antihypertensive or analgesic medications. Physical examination showed a well-developed woman whose weight was 62.5 kg. Blood pressure was 130/96 mm Hg. Her abdomen was markedly protuberant, due to large abdominal masses. Her waist was 100 cm in circumference, and her mid-abdominal girth measurement was 114 cm. There was I + pretibial edema bilaterally. Her admission laboratory studies showed a blood urea nitrogen (BUN) of 6.8 mmol/L (19 mg/dL), serum creatinine 79.6 /Lmol/L (0.9 mg/dL), serum albumin 38 g/L (3.8 gfdL); hematocrit 45%; and urinalysis, which showed no protein or casts. There were 4 to 5 white blood cells per high-
power field, but urine culture and sensitivity showed no bacterial growth. A computerized tomography (CT) scan of her abdomen confirmed massively enlarged kidneys bilaterally due to the presence of enormous cysts, occupying most of the abdomen and distorting other intra-abdominal structures. The CT scan confirmed a right kidney greater than 23 cm in length, and a left kidney greater than 24 cm in length. After obtaining informed consent, a bilateral cyst reduction operation was performed through a midline incision extending from the xiphoid process to the pubis. The peritoneal cavity was entered and the right and left colons were reflected medially to expose the kidneys for unroofing of the cysts. Several of the larger cysts were aspirated, including 3,050 mL from a single cyst in the left kidney, as well as 540 mL, 270 mL, 210 mL, and 130 mL from individual cysts in that same kidney. A total of 7,600 mL of cyst fluid was collected from the two kidneys. Superficial cysts were unroofed with electrocautery, and through the cavities of the unroofed cysts, the domes of deeper cysts were also unroofed. Following completion of cyst decompression, bilateral suction drains were placed posterior to the kidneys in the retroperitoneum. During surgery, the patient received I U of autologous whole blood, 2 L of crystalloid solution, and 25 g of mannitol. Estimated blood loss at surgery was 250 mL. At the time of closure, her mid-waist girth was 83.8 cm and her mid-abdominal girth at its greatest point was 90.2 cm. Preoperative and postoperative appearance of the patient's abdomen and her CT scans are shown in Figs I and 2. The patient had a relatively smooth postoperative course. However, she did require 2 to 3 L of crystalloid for the first 2 to 3 days postoperatively to maintain her systolic blood pressure at 110 mm Hg. She was discharged from the hospital on the ninth postoperative day with a BUN of 2.5 mmol/L (7 mg!dL) and a serum creatinine of 70.7 /Lmol/L (0.8 mg! dL). Her discharge weight was 48.9 kg. Follow-up at I month showed an endogenous creatinine clearance of 1.75 mL/s (105 mL/min), a stable blood pressure of 120/82 mm Hg, and complete relief of symptoms of abdominal pain and discomfort. She was active, playing tennis, and without symptoms. She did require repair of an incisional hernia 9 months after surgery. A 3-year follow-up shows continued relief of pain without increase in abdominal girth and normal blood pressure From the Departments of Medicine and Urology, Oregon Health Sciences University, Portland, OR. Address reprint requests to William M. Bennett, MD, L463 Division of Nephrology, Oregon Health Sciences University, Portland, OR 97201. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/1901-0017$3.00;0
American Journal of Kidney Diseases, Vol XIX, No 1 (January), 1992: pp 89-92
89
ELZINGA, BARRY, AND BENNETT
90
but in individual cases, pain can be severe with cysts that are only moderate in size. Mild, nonnarcotic analgesics suffice in most patients. There is a subgroup of APKD patients who develop refractory, disabling pain so severe that they require narcotic analgesics for relief. In such individuals, more radical approaches have been considered. Relief of symptoms by cyst decompression was first reported by Rovsing in 1911. 2 Despite many reports of impressive relief of pain by surgical decompression, emptying of cysts by needle puncture or actual removal of cyst walls, allowing drainage of fluid into the abdomen, was abandoned in the late 1950s, primarily because of the report by Bricker and Patton of two patients who developed decreased glomerular filtration rate with surgical decompression. 3 It was the contention of these investigators that cyst reduction surgery should be abandoned because of the potential loss of functioning cystic nephrons by the surgical procedure itself. It should be noted in
Fig 1. Preoperative (top) and postoperative (bottom) views of the patient's abdomen.
without medications. Serum creatinine was 88.4 ILmol/L (1 mgjdL) at 3 years, with a creatinine clearance of 1.66 mL/s (99.4 mL/min).
Questions I. What is the role of cyst reduction surgery in providing symptomatic relief of pain in patients with ADPKD? 2. What effect does cyst reduction surgery have on renal function in patients with ADPKD?
DISCUSSION
Abdominal pain is a common symptom in patients with autosomal dominant polycystic kidney disease. Usually, the pain is dull and constant, localizing to the flank or lateral abdomen. At times it may be colicky and sharp, and the alert clinician needs to keep in mind that obstruction of the ureter due to a large cyst, blood clot, stone, or neoplasm can produce pain that is superimposed on the chronic pain of patients with polycystic kidney disease. In the classical, longitudinal studies of Dalgaard, pain gradually increasing over a patient's lifetime ultimately affected more than 50% of individuals. 1 Pain, when present, has a general relationship with the size of the kidneys,
Fig 2. CT scans before (top) and after (bottom) cyst reduction surgery.
SURGICAL TREATMENT OF POLYCYSTIC KIDNEYS
reviewing that report that one of the patients actually had a transient improvement in kidney function, and the rate of renal functional decline before surgery was not specified. In 1980, Shangzhi et al reported encouraging long-term pain relief in a group of 52 patients, who had been operated on because of symptomatic polycystic kidney disease. 4 In the Chinese experience, pain relief was striking with no loss of kidney function. We decided to reexamine surgical cyst decompression in a group of patients, such as the present case, who were referred for refractory pain management. 5 Ultrasound-guided percutaneous aspiration of cyst fluid from the largest cysts on the side or sides affected was first accomplished without complications. All patients experienced dramatic pain relief, but in most patients the duration of that relief was transient. The actuarial probability of a patient being pain-free 18 months after cyst aspiration alone was 33% ± 17%. Using the recurrence of pain within 6 months following cyst aspiration as an indication for surgery, we reported that six patients received impressive pain relief" with a probability of a patient being painfree 18 months after surgery of 81 % ± 12%. 5 There was no loss of kidney function after either aspiration or surgery. The question of recurrence of large cysts after surgical decompression has not been addressed in any systematic manner. Some centers instill alcohol as a sclerosing agent to prevent secretion of fluid and reoccurrence of the cysts. This has not been a problem in our clinical experience and the maintenance of pain relief over long periods of time has been excellent, as illustrated by the present case. The question of the effects of surgery on renal function is more difficult to answer. Initially, it was proposed that removal of cysts and cyst fluid would contribute to the overall decline in glomerular filtration rate. However, even on theoretical grounds, the loss of several hundred cystic nephrons should make little difference to whole kidney function, since the adult kidney has approximately 1 million nephrons and only 2% to 10% are cystic. Further, if renal dysfunction is produced by the pressure of cysts on adjacent normal parenchyma, it is possible that reduction of cyst volume might actually result in renal functional improvement. Our case demonstrated a 20% to 25% improvement in kidney function,
91
which has been maintained over 3 years. It is impossible to say whether this was a result of the surgery. Furthermore, in a large experience with surgical reduction of cyst volume in patients from the Mayo Clinic and Oregon Health Sciences University, no change in the slope of the l/creatinine line can be demonstrated as a result of this surgical procedure. 6 This is somewhat different from the more optimistic reports of the Chinese investigators. It is possible that more extensive surgery, with removal of more cysts, would be beneficial, or alternatively, that the cyst surgery has no beneficial effect. Certainly, contrary to the predictions of Bricker and Patton in the 1950s, marked deterioration in renal function, which was the major reason that the surgical procedures were abandoned, has not been experienced. A careful review of the literature on the effects of cyst reduction surgery, showed little adverse and many favorable outcomes on renal function in the period of time between 1911 and 1960. 7 This experience is all the more remarkable because most of the surgery was performed before the availability of routine dialysis and modern antibiotics. Nearly all the fatalities following surgical decompression had advanced preoperative renal failure or postoperative infections. At the present time, improvement of renal function cannot be used as an indication for performing cyst-reduction surgery, based on any data available in the literature. However, in patients with refractory symptoms, one can be relatively confident with an experienced surgical team, that renal functional decline will not result directly due to the surgical procedure. In our hands, the relief of symptoms is impressive. One final benefit of a surgical approach might be amelioration of high blood pressure, which is known to cause acceleration of renal functional decline in polycystic kidney disease. The present patient was mildly hypertensive before surgery and has not required antihypertensive medicine or experienced elevated diastolic blood pressures since the surgical procedure 3 years ago. There is also reported experience in the literature of improvement in blood pressure control with cyst reduction surgery. An extensive review of previous experience with cyst reduction surgery has been published. 7 Thus, it can be concluded from this case that appropriate patients with refractory symptoms may be benefited by a reduction of cyst volume
92
ELZINGA, BARRY, AND BENNETI
by aspiration or surgery. It is our preference to perform cyst aspiration oflarger cysts to give the patient an idea of the type of symptomatic relief that can be expected from more extensive surgery. We then operate on patients in whom symptoms
recur following the aspiration. We occasionally are surprised by patients who obtain prolonged, and in one case permanent, relief of symptoms with a single cyst aspiration under ultrasound guidance.
REFERENCES 1. Dalgaard OZ: Bilateral polycystic disease of the kidneys: A follow-up study of 284 patients and their families. Acta Med Scand 158:1-255, 1957 (suppl 328) 2. Rovsing T: Treatment of multilocular renal cyst with multiple punctures. Hospitaistad 4: 105, 1911 3. Bricker NS, Patton JF: Renal function studies in polycystic disease of the kidney with observations on the effect of surgical decompression. N Eng! J Med 256:212-214, 1957 4. Shangzhi H, Shiyuan A, Henning J, et ai: Cyst decapitating decompression operation in polycystic kidneys. Chinese Med J 93:773-778, 1980
5. Bennett WM, Elzinga L, Golper TA, et al: Reduction of cyst volume for symptomatic management of autosomal dominant polycystic kidney disease. J Urol 137:620-625, 1987 6. Elzinga L, Barry J, Torres V, et al: Cyst decompression surgery for autosomal dominant polycystic kidney disease. Kid Int 37:247, 1990 (abstr) 7. Bennett WM, Elzinga LW, Barry JM: Management of cystic kidney disease, in Gardner KD, Bernstein J (eds): The Cystic Kidney. Dordrecht, Netherlands, Kluwer, \990, pp 247275
![[Autosomal-dominant polycystic kidney disease].](/assets/img/hold.png)
