- Email: [email protected]
Pain management in polycystic kidney disease
Pain Management in Polycystic Kidney Disease Related Article, p. 720
B
OTH ACUTE AND chronic pain is a common complaint in patients with autosomal dominant polycystic kidney disease (ADPKD) and afflicts about 60% of the 600,000 patients in the United States (prevalence is approximately 1 in every 1,000 live deliveries) with an established diagnosis.1 This most common of genetic diseases results in end-stage renal disease (ESRD) developing in approximately 50% of patients by 60 years of age. The spectrum of pain in patients with ADPKD may be related directly to renal cyst growth or complications caused by the massive cysts. To understand the pain patterns noted in patients with ADPKD, it is important to appreciate the diverse nerve supply to the kidneys. The kidneys and ureters are well supplied by sympathetic, parasympathetic, and sensory afferent fibers. The sympathetic supply to the kidney comes from the aorticorenal and celiac ganglia originating in spinal cord segments T9-T11 as well as from the cephalad portion of the lumbar sympathetic trunk. The postganglionic sympathetic nerves from the aorticorenal and celiac plexi also join in the renal pelvis. These nerves thus distribute to and innervate the vascular musculature and smooth muscles of the renal calyces and renal pelvis. They also extend along the afferent arterioles all the way to the juxtaglomurular apparatus.2 The parasympathetic innervation of the kidneys originates from the vagus nerve, supplying the muscles in the renal pelvis and calyces, but not the parenchyma of the kidneys. Sensory innervation of the kidneys comes from the 10th through 12th thoracic spinal nerves, which pass through the thoracic sympathetic ganglia, then travel via the splanchnic nerves to the renal plexus, and then travel to the kidneys.2 Although gross hematuria is thought to be most commonly caused by cyst rupture, such bleeding can also be related to the increased
娀 2000 by the National Kidney Foundation, Inc. 0272-6386/00/3504-0034$3.00/0 770
incidence of urinary tract infections and nephrolithiasis in patients with ADPKD. Therefore, the presentation of abdominal/flank pain and hematuria must result in a consideration of these three conditions in the differential diagnosis.3,4 Rupture of cysts with hemorrhage into the tract leads to gross hematuria and flank pain.5 It is estimated that between 43% and greater than 50% of patients with ADPKD will have hematuria related to hemorrhage of a renal cyst. Hemorrhage into a cyst without gross hematuria occurs if the cyst does not communicate with the urinary tract. The frequency of hematuria from cyst rupture correlates directly with the size of the kidney. The incidence of hematuria seems to increase dramatically when one or both kidneys is larger than 15 cm.6-8 These episodes tend to resolve spontaneously with conservative management over 2 to 3 days. However, persistent bleeding has been noted to occur for weeks despite bed rest and vigorous hydration. Long-term prognosis, with regards to the development of progressive renal failure, is worse in PKD patients who have episodes of gross hematuria when compared with patients without this complication. Cyst rupture on the surface of the kidney can lead to a subcapsular hematoma. Pain under this circumstance is usually of a mild steady quality, occurring in the flank and persisting until the hematoma has been absorbed. Infection developing within a cyst can mimic pyelonephritis. The presence of fever helps to differentiate pain related to infection from that caused by hemorrhage, because fever is not a common accompaniment to hematuria secondary to cyst rupture.9 Nephrolithiasis is a common complication of ADPKD and occurs in approximately 20% of this patient population.10 Uric acid stones account for up to 50% of stones in PKD patients, a much higher incidence than in the general population. This increase in the incidence of stone formation may be due to hyperoxaluria, hyperuricosuria, and hypocitraturia in the face of renal tubular stasis. Because of the compressed and distorted calices, treatment modalities such as ureteroscopy, extracorporeal shock wave lithotripsy, and nephrolithotomy are more difficult in patients with ADKPD.11 Chronic pain related to ADPKD can frequently be caused by mechanical back pain. Our
American Journal of Kidney Diseases, Vol 35, No 4 (April), 2000: pp 770-772
EDITORIAL
unpublished observation in a cohort of patients with documented ADPKD for 10 years or greater notes that there is an average 4-cm hypertrophy of the lumbodorsal muscles on magnetic resonance imaging as compared with age- and gendermatched controls without ADPKD. Compensatory hypertrophy correlates directly with renal cyst volume. Low back pain can occur because of the lumbar lordosis that slowly occurs due to a change in the pelvic tilt related to enlarging cysts. Because bilaterial cyst enlargement can be asymmetric, the pelvic shift in posture can produce low back pain localized on one side more than the other. This chronic alteration in posture appears to accelerate the development of disc disease in the lumbosacral region. When polycystic liver disease compounds the picture, the postural changes become more pronounced and subsequent back pain can be debilitating. In addition, patients with ADPKD have an increased incidence of spinal stenosis and lumbosacral radiculopathly due to disc disease or degenerative spine disease.12,13 Chronic pain can be related directly to cyst formation because of cyst compression on the surrounding tissues, leading to traction on the pedicle of the kidney and the subsequent distention of the renal capsule. Standing and walking exacerbate the pain, which generally correlates with the size of the kidneys, but there are some marked exceptions. Patients can frequently localize the source of pain with one finger, with an anterior abdominal location being more common than generalized back pain. With massive cyst formation, early satiety can occur due to the compression of the greater curvature of the stomach and/or duodenal loop. Pain related to enlarging cysts does not correlate with the level of renal function. When pain is the predominant complaint, it begins early in the course of demonstrable cyst formation. A detailed history is necessary before approaching the management of pain in a methodical, stepwise fashion. Using charts to localize pain is a helpful maneuver. Most physicians tend to jump to narcotic analgesics because of their discomfort analyzing the cause for the chronic pain syndrome. The following approaches should be taken in a stepwise sequence: (1) systemic analgesics; (2) physical measures such as acupuncture, ice massage, and heating pads; (3)
771
transcutaneous electrical nerve stimulation; (4) autonomic plexus blockade; (5) acupuncture; (6) psychobehaviorial measures; (7) neuromodulation by spinal cord stimulation; (8) neuraxial opiodes and local anethestics; (9) surgical decompression of kidney and liver cysts; and (10) nephrectomy and hepatectomy (partial). The article by Dunn et al14 in this issue of the Journal outlines a new addition to the armamentarium of therapeutic modalitites. Laproscopic nephrectomy in skilled hands does decrease morbidity and is also a cost-saving measure. Patient selection for this procedure will depend on surgical expertise with laproscopic nephrectomy, but it should be the last step taken in the approach to pain control. Because physicians will generally try systemic analgesics before referring a patient to a pain clinic, a step ladder approach for pharmacological therapy of pain is as noted. Acetaminophen should be the first drug used, being effective in mild to moderate pain. In the majority of patients, pain can be successfully managed with currently available management techniques and careful elucidation of the underlying multifactorial causes of pain. Patients with complex pain problems may benefit from referral to a multidisciplinary pain center where a variety of medical, psychological, and interventional therapies are available. —Theodore I. Steinman, MD Director, Dialysis Unit – BIDMC Professor of Medicine Harvard Medical School Boston, Massachusetts REFERENCES 1. Reeders S, Germino GG: The molecular genetics of autosomal dominant polycystic kidney disease. Semin Nephrol 9:122-134, 1989 2. Bonica JJ: Diseases of the kidney and ureter, in Bonica JJ (ed): The Management of Pain (ed 2). Philadelphia, PA, Lea & Febiger, 1990, pp 1232-1249 3. Milutinovic J, Philip J, Fialkow P, Agodoa L, Philip L, Rudd T, Sutherland S: Clinical manifestations of autosomal dominant polycystic kidney diseases in patients older than 50 years. Am J Kidney Dis 15:237-243, 1990 4. Gabow PA: Autosomal dominant polycystic kidney disease, more than a renal disease. Am J Kidney Dis 16:403413, 1990 5. Bennett W, Elzinga L, Barry J: Polycystic kidney disease: Diagnosis and management. Hospital Practice 4:6172, 1992
772
6. Bennett WM, Elzinga LW: Clinical management of autosomal dominant polycystic kidney disease. Kidney Int 44:S74-S79, 1993 (suppl 42) 7. Rovitch L, Lerman PH, Drabkin J: Ruptured renal cysts in polycystic kidney disease. Urology 7:60-61, 1976 8. Anderson GA, Degroot D, Lawson RK: Polycystic renal disease. Urology 42:358-364, 1993 9. Sklar AH, Caruana RJ, Lamers JE, Stauser GD: Renal infections in patients with adult polycystic kidney disease. Am J Kidney Dis 10:81-88, 1987 10. Torres VE, Erickson SB, Smith LH, Wilson DM, Hattery RR, Segura JW: The association of nephrolithiasis and autosomal dominant polycystic kidney disease. Am J Kidney Dis 11:318-325, 1988 11. Van Laecke E, Oosterlinck W: Physiopathology of
THEODORE I. STEINMAN
renal colic and therapeutic consequences. Acta Urol Belgica 62:15-18, 1994 12. Benzon HT: Epidural steroid injections for low back pain and lumbosacral radiculopathy. Pain 24:277-295, 1986 13. Breivik H, Hesla PE, Molnar I, Lind B: Treatment of chronic low back pain and sciatica: Comparison of caudal epidural injections of bupivacaine and methylprednisolone with bupivacaine followed by saline. Adv Pain Res Ther 1:927-932, 1977 14. Dunn MD, Portis AJ, Elbahnasy AM, Shalhav AL, Rothstein M, McDougall EM, Clayman RV: Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease. Am J Kidney Dis 35:720-725, 2000
B
OTH ACUTE AND chronic pain is a common complaint in patients with autosomal dominant polycystic kidney disease (ADPKD) and afflicts about 60% of the 600,000 patients in the United States (prevalence is approximately 1 in every 1,000 live deliveries) with an established diagnosis.1 This most common of genetic diseases results in end-stage renal disease (ESRD) developing in approximately 50% of patients by 60 years of age. The spectrum of pain in patients with ADPKD may be related directly to renal cyst growth or complications caused by the massive cysts. To understand the pain patterns noted in patients with ADPKD, it is important to appreciate the diverse nerve supply to the kidneys. The kidneys and ureters are well supplied by sympathetic, parasympathetic, and sensory afferent fibers. The sympathetic supply to the kidney comes from the aorticorenal and celiac ganglia originating in spinal cord segments T9-T11 as well as from the cephalad portion of the lumbar sympathetic trunk. The postganglionic sympathetic nerves from the aorticorenal and celiac plexi also join in the renal pelvis. These nerves thus distribute to and innervate the vascular musculature and smooth muscles of the renal calyces and renal pelvis. They also extend along the afferent arterioles all the way to the juxtaglomurular apparatus.2 The parasympathetic innervation of the kidneys originates from the vagus nerve, supplying the muscles in the renal pelvis and calyces, but not the parenchyma of the kidneys. Sensory innervation of the kidneys comes from the 10th through 12th thoracic spinal nerves, which pass through the thoracic sympathetic ganglia, then travel via the splanchnic nerves to the renal plexus, and then travel to the kidneys.2 Although gross hematuria is thought to be most commonly caused by cyst rupture, such bleeding can also be related to the increased
娀 2000 by the National Kidney Foundation, Inc. 0272-6386/00/3504-0034$3.00/0 770
incidence of urinary tract infections and nephrolithiasis in patients with ADPKD. Therefore, the presentation of abdominal/flank pain and hematuria must result in a consideration of these three conditions in the differential diagnosis.3,4 Rupture of cysts with hemorrhage into the tract leads to gross hematuria and flank pain.5 It is estimated that between 43% and greater than 50% of patients with ADPKD will have hematuria related to hemorrhage of a renal cyst. Hemorrhage into a cyst without gross hematuria occurs if the cyst does not communicate with the urinary tract. The frequency of hematuria from cyst rupture correlates directly with the size of the kidney. The incidence of hematuria seems to increase dramatically when one or both kidneys is larger than 15 cm.6-8 These episodes tend to resolve spontaneously with conservative management over 2 to 3 days. However, persistent bleeding has been noted to occur for weeks despite bed rest and vigorous hydration. Long-term prognosis, with regards to the development of progressive renal failure, is worse in PKD patients who have episodes of gross hematuria when compared with patients without this complication. Cyst rupture on the surface of the kidney can lead to a subcapsular hematoma. Pain under this circumstance is usually of a mild steady quality, occurring in the flank and persisting until the hematoma has been absorbed. Infection developing within a cyst can mimic pyelonephritis. The presence of fever helps to differentiate pain related to infection from that caused by hemorrhage, because fever is not a common accompaniment to hematuria secondary to cyst rupture.9 Nephrolithiasis is a common complication of ADPKD and occurs in approximately 20% of this patient population.10 Uric acid stones account for up to 50% of stones in PKD patients, a much higher incidence than in the general population. This increase in the incidence of stone formation may be due to hyperoxaluria, hyperuricosuria, and hypocitraturia in the face of renal tubular stasis. Because of the compressed and distorted calices, treatment modalities such as ureteroscopy, extracorporeal shock wave lithotripsy, and nephrolithotomy are more difficult in patients with ADKPD.11 Chronic pain related to ADPKD can frequently be caused by mechanical back pain. Our
American Journal of Kidney Diseases, Vol 35, No 4 (April), 2000: pp 770-772
EDITORIAL
unpublished observation in a cohort of patients with documented ADPKD for 10 years or greater notes that there is an average 4-cm hypertrophy of the lumbodorsal muscles on magnetic resonance imaging as compared with age- and gendermatched controls without ADPKD. Compensatory hypertrophy correlates directly with renal cyst volume. Low back pain can occur because of the lumbar lordosis that slowly occurs due to a change in the pelvic tilt related to enlarging cysts. Because bilaterial cyst enlargement can be asymmetric, the pelvic shift in posture can produce low back pain localized on one side more than the other. This chronic alteration in posture appears to accelerate the development of disc disease in the lumbosacral region. When polycystic liver disease compounds the picture, the postural changes become more pronounced and subsequent back pain can be debilitating. In addition, patients with ADPKD have an increased incidence of spinal stenosis and lumbosacral radiculopathly due to disc disease or degenerative spine disease.12,13 Chronic pain can be related directly to cyst formation because of cyst compression on the surrounding tissues, leading to traction on the pedicle of the kidney and the subsequent distention of the renal capsule. Standing and walking exacerbate the pain, which generally correlates with the size of the kidneys, but there are some marked exceptions. Patients can frequently localize the source of pain with one finger, with an anterior abdominal location being more common than generalized back pain. With massive cyst formation, early satiety can occur due to the compression of the greater curvature of the stomach and/or duodenal loop. Pain related to enlarging cysts does not correlate with the level of renal function. When pain is the predominant complaint, it begins early in the course of demonstrable cyst formation. A detailed history is necessary before approaching the management of pain in a methodical, stepwise fashion. Using charts to localize pain is a helpful maneuver. Most physicians tend to jump to narcotic analgesics because of their discomfort analyzing the cause for the chronic pain syndrome. The following approaches should be taken in a stepwise sequence: (1) systemic analgesics; (2) physical measures such as acupuncture, ice massage, and heating pads; (3)
771
transcutaneous electrical nerve stimulation; (4) autonomic plexus blockade; (5) acupuncture; (6) psychobehaviorial measures; (7) neuromodulation by spinal cord stimulation; (8) neuraxial opiodes and local anethestics; (9) surgical decompression of kidney and liver cysts; and (10) nephrectomy and hepatectomy (partial). The article by Dunn et al14 in this issue of the Journal outlines a new addition to the armamentarium of therapeutic modalitites. Laproscopic nephrectomy in skilled hands does decrease morbidity and is also a cost-saving measure. Patient selection for this procedure will depend on surgical expertise with laproscopic nephrectomy, but it should be the last step taken in the approach to pain control. Because physicians will generally try systemic analgesics before referring a patient to a pain clinic, a step ladder approach for pharmacological therapy of pain is as noted. Acetaminophen should be the first drug used, being effective in mild to moderate pain. In the majority of patients, pain can be successfully managed with currently available management techniques and careful elucidation of the underlying multifactorial causes of pain. Patients with complex pain problems may benefit from referral to a multidisciplinary pain center where a variety of medical, psychological, and interventional therapies are available. —Theodore I. Steinman, MD Director, Dialysis Unit – BIDMC Professor of Medicine Harvard Medical School Boston, Massachusetts REFERENCES 1. Reeders S, Germino GG: The molecular genetics of autosomal dominant polycystic kidney disease. Semin Nephrol 9:122-134, 1989 2. Bonica JJ: Diseases of the kidney and ureter, in Bonica JJ (ed): The Management of Pain (ed 2). Philadelphia, PA, Lea & Febiger, 1990, pp 1232-1249 3. Milutinovic J, Philip J, Fialkow P, Agodoa L, Philip L, Rudd T, Sutherland S: Clinical manifestations of autosomal dominant polycystic kidney diseases in patients older than 50 years. Am J Kidney Dis 15:237-243, 1990 4. Gabow PA: Autosomal dominant polycystic kidney disease, more than a renal disease. Am J Kidney Dis 16:403413, 1990 5. Bennett W, Elzinga L, Barry J: Polycystic kidney disease: Diagnosis and management. Hospital Practice 4:6172, 1992
772
6. Bennett WM, Elzinga LW: Clinical management of autosomal dominant polycystic kidney disease. Kidney Int 44:S74-S79, 1993 (suppl 42) 7. Rovitch L, Lerman PH, Drabkin J: Ruptured renal cysts in polycystic kidney disease. Urology 7:60-61, 1976 8. Anderson GA, Degroot D, Lawson RK: Polycystic renal disease. Urology 42:358-364, 1993 9. Sklar AH, Caruana RJ, Lamers JE, Stauser GD: Renal infections in patients with adult polycystic kidney disease. Am J Kidney Dis 10:81-88, 1987 10. Torres VE, Erickson SB, Smith LH, Wilson DM, Hattery RR, Segura JW: The association of nephrolithiasis and autosomal dominant polycystic kidney disease. Am J Kidney Dis 11:318-325, 1988 11. Van Laecke E, Oosterlinck W: Physiopathology of
THEODORE I. STEINMAN
renal colic and therapeutic consequences. Acta Urol Belgica 62:15-18, 1994 12. Benzon HT: Epidural steroid injections for low back pain and lumbosacral radiculopathy. Pain 24:277-295, 1986 13. Breivik H, Hesla PE, Molnar I, Lind B: Treatment of chronic low back pain and sciatica: Comparison of caudal epidural injections of bupivacaine and methylprednisolone with bupivacaine followed by saline. Adv Pain Res Ther 1:927-932, 1977 14. Dunn MD, Portis AJ, Elbahnasy AM, Shalhav AL, Rothstein M, McDougall EM, Clayman RV: Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease. Am J Kidney Dis 35:720-725, 2000