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Secondary polycythemia caused by ureteropelvic junction obstruction successfully treated by laparoscopic nephrectomy
CASE REPORT
SECONDARY POLYCYTHEMIA CAUSED BY URETEROPELVIC JUNCTION OBSTRUCTION SUCCESSFULLY TREATED BY LAPAROSCOPIC NEPHRECTOMY RALPH MADEB, JOY KNOPF, CRAIG NICHOLSON, RONALD RABINOWITZ,
AND
ERDAL ERTURK
ABSTRACT Secondary polycythemia is a condition that causes an increase in red blood cell count either because of the physiologic response to stress or inappropriate secretion of erythropoietin. We report a case of a secondary polycythemia caused by ureteropelvic junction obstruction that was successfully treated by laparoscopic nephrectomy. UROLOGY 67: 1291.e1–1291.e3, 2006. © 2006 Elsevier Inc.
S
econdary polycythemia is a condition caused by an increase in red blood cell count either because of a physiologic response to stress or an inappropriate secretion of erythropoietin.1,2 The hallmark of a patient with polycythemia is an elevation in absolute red blood cell count, hematocrit (more than 48% in women or 52% in men), or hemoglobin concentration (greater than 16.5 g/dL in women or 18.5 g/dL in men). Secondary polycythemia is most often due to an oxygen-sensitive erythropoietin response to hypoxia.1,3 It can also present as a paraneoplastic response in the presence of an erythropoietin-secreting tumor.4,5 In rare cases, cobalt exposure, dysregulated angiotensin-feedback mechanisms, such as that seen in post-renal transplant patients, and elevated levels of insulin-like growth factor-1, have also been shown to stimulate erythropoiesis and cause secondary polycythemia.2,6,7 We report a rare case of secondary polycythemia caused by massive hydronephrosis from ureteropelvic junction (UPJ) obstruction that was successfully treated with laparoscopic nephrectomy. CASE REPORT A 24-year-old healthy man had hypertension of 145/98 mm Hg during a routine annual examination. The patient’s physical examination was unreFrom the Department of Urology, University of Rochester Medical Center, Rochester, New York Address for correspondence: Ralph Madeb, M.D., Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642. E-mail: Ralph_ [email protected] Submitted: February 11, 2005, accepted (with revisions): December 19, 2005 © 2006 ELSEVIER INC. ALL RIGHTS RESERVED
markable; however, screening laboratory examinations demonstrated an elevated hematocrit of 64%. All other laboratory testing was within normal limits. The patient was referred to a hematologist for his newly diagnosed polycythemia. The patient denied any familial hematologic disorders, did not smoke, or have any sleep disorders. After additional hematologic testing excluded primary polycythemia, rare familial disorders, and polycythemia vera, the patient was sent for computed tomography for workup of secondary causes of polycythemia, including renal diseases or tumors with ectopic erythropoietin production. Computed tomography of the abdomen and pelvis demonstrated a chronic UPJ obstruction with a massively hydronephrotic right kidney bulging into the right lobe of the liver (Fig. 1). The patient was immediately started on serial phlebotomies, allowing his hematocrit to drop to only 52%. The patient was then referred to our department for definitive management of his chronic UPJ obstruction. The patient underwent uncomplicated laparoscopic nephrectomy. The final pathologic examination revealed medullary and cortical atrophy with fibrosis and mild interstitial nephritis consistent with chronic obstruction. Postoperatively, the patient had no complications, and 4 weeks after his surgery his hematocrit was 46% without the need for subsequent phlebotomies. At 8 weeks postoperatively, the patient’s hematocrit had equilibrated at 41% without further evidence of secondary polycythemia. COMMENT Polycythemia is a blood disorder characterized by an increase in the number of red blood cells in 0090-4295/06/$32.00 doi:10.1016/j.urology.2005.12.042 1291.e1
FIGURE 1. Computed tomography scan demonstrating massively hydronephrotic right kidney bulging into right lobe of liver.
the circulation.1,2 It includes a wide variety of disorders and can be categorized as either primary or secondary. Primary polycythemia is caused by myeloproliferative disorders (eg, polycythemia vera) or by rare familial genetic disorders1,2,8 Secondary polycythemia develops in response to a known hypoxic stimulus or abnormal production of erythropoietin. Erythropoietin is the main hormone regulating red blood cell production, and its serum level increases exponentially in response to anemia or other hypoxic stimuli.1,2,9 Although certain pathologic states may also result in increased erythropoietin, hypoxia is the only physiologic stimulus known to cause an increase in erythropoietin levels.9 Adaptation to hypoxia is critical for survival, and hypoxia sensing provides the impetus for various mechanisms ensuring maintenance of oxygen homeostasis. The activation of the hypoxia sensing mechanisms results in the subsequent activation of an array of genes, including those implicated in glucose metabolism, vasculogenesis, iron transport, and erythropoiesis. Polycythemia has been reported in association with kidney lesions such as Wilms’ tumor (adult and children), polycystic kidneys, and in lesions associated with the von Hippel-Lindau syndrome (renal cell carcinoma, renal hemangioma, pheochromocytoma).10 It has also been reported as a frequent complication after kidney transplantation, an entity known as post-transplant erythrocytosis, which occurs in up to 20% of renal transplant recipients.11 Secondary polycythemia has also been described as a paraneoplastic syndrome in renal cell carcinoma.4,5,12 This is believed to occur owing to increased production of erythropoietin either directly by the tumor or by the adjacent nor1291.e2
mal parenchyma in response to the hypoxia induced by tumor growth. Rarely, hydronephrosis and postrenal obstruction have been reported as the cause of secondary polycythemia.4,5,12–14 Although the overall incidence of erythrocytosis in patients with renal pathologic findings has not been defined, it has been reported as a paraneoplastic syndrome in 1% to 5% of patients with renal cell carcinoma, and approximately 4% of patients with erythrocytosis have renal cell carcinoma,4,12,15 especially those with large tumors. Patients with renal cell carcinoma and erythrocytosis do not necessarily have an elevated serum erythropoietin concentration. However, in patients without other causes of erythrocytosis, successful surgical removal of the renal pathologic features results in resolution of the polycythemia.13,14 Thus, to favorably affect the clinical outcome, it is important to precisely define the causes of polycythemia for each patient and treat them appropriately. To elucidate its cause, it is crucial that all patients who exhibit polycythemia undergo appropriate imaging to look for a curable cause of this disorder. Careful examination of the kidneys is mandatory to detect renal lesions that may be responsible for the polycythemia, such as was the case with our patient. Abdominal imaging by ultrasonography or computed tomography can detect the presence of underlying liver or renal pathologic features. In this instance, a large and rare renal abnormality was disclosed during the appropriate workup for an unknown cause of erythrocytosis. We believe that the chronic UPJ obstruction in our patient caused severe hydronephrosis with a resulting increase in erythropoietin secondary to local renal ischemia. In addition, the severe hydronephrosis with displacement of the kidney may have also contributed to the renal ischemia by encroaching on and displacing the branches of the renal artery. By relieving the obstruction with laparoscopic nephrectomy, the stimulus for erythropoietin production was removed, thus allowing the patient’s hematocrit to settle in the normal range without the need for additional invasive and morbid phlebotomies. Although cases of polycythemia caused by UPJ obstruction have been previously reported, and improvement after open nephrectomy has been described,12–15 this is the first account of definitive treatment of secondary polycythemia with laparoscopic nephrectomy. Moreover, this case has demonstrated that no difference results in the clinical outcome, regardless of the manner in which the etiology is removed—whether by the open or laparoscopic approach. Rather, it is the accurate diagnosis and timely management that most affects patient outcome. UROLOGY 67 (6), 2006
CONCLUSIONS Secondary polycythemia due to chronic UPJ obstruction, although rare, can occur and can be cured by the less-invasive approach of laparoscopic nephrectomy. REFERENCES 1. Berlin NI: Diagnosis and classification of the polycythemias. Semin Hematol 12: 339 –351, 1975. 2. Prchal JT: Classification and molecular biology of polycythemias (erythrocytoses) and thrombocytosis. Hematol Oncol Clin North Am 17: 1151–1158, 2003. 3. Jelinek J, and Prchal JT: Oxygen-dependent regulation of erythropoiesis. Methods Enzymol 381: 201–210, 2004. 4. Gross AJ, Wolff M, Fandrey J, et al: Prevalence of paraneoplastic erythropoietin production by renal cell carcinomas. Clin Invest 72: 337–340, 1994. 5. Mirand EA, Murphy GP, Steeves RA, et al: Extra-renal production of erythropoietin in man. Acta Haematol 39: 359 – 365, 1968. 6. Gregg XT, Reddy V, and Prchal JT: Copper deficiency masquerading as myelodysplastic syndrome. Blood 100: 1493– 1495, 2002. 7. Mok H, Jelinek J, Pai S, et al: Disruption of ferroprotein 1 regulation causes dynamic alterations in iron homeosta-
UROLOGY 67 (6), 2006
sis and erythropoiesis in polycythaemia mice. Development 131: 1859 –1868, 2004. 8. Gordeuk VR, Stockton DW, and Prchal JT: Congenital polycythemias/erythrocytoses. Haematologica 90: 109 –116, 2005. 9. Prchal JT, and Pastore YD: Erythropoietin and erythropoiesis: polycythemias due to disruption of oxygen homeostasis. Hematol J 5(suppl 3): S110 –S113, 2004. 10. Pastore Y, Jedlickova K, Guan Y, et al: Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. Am J Hum Genet 73: 412– 419, 2003. 11. Hilbrands LB, Hoitsma AJ, and Koene RA: Post-transplant haemoglobin levels and host kidney status. Transpl Int 5(suppl 1): S73–S74, 1992. 12. Murphy GP, Mirand EA, Johnston GS, et al: Erythropoietin alterations in human genitourinary disease states: correlation with experimental observations. J Urol 99: 802– 810, 1968. 13. Bailey RR, Shand BI, and Walker RJ: Reversible erythrocytosis in a patient with a hydronephrotic horseshoe kidney. Nephron 70: 104 –105, 1995. 14. Narayana AS, Gallagher F, Kelly DG, et al: Hydronephrosis and polycythaemia. Br J Urol 48: 175–176, 1976. 15. Novick AC, and Campbell SC: Renal tumors, in Walsh PC, Retik AB, Vaughan ED, et al (Eds): Campbell’s Urology, 8th ed. Philadelphia, WB Saunders, 2002, vol 4, pp 2672–2731.
1291.e3
SECONDARY POLYCYTHEMIA CAUSED BY URETEROPELVIC JUNCTION OBSTRUCTION SUCCESSFULLY TREATED BY LAPAROSCOPIC NEPHRECTOMY RALPH MADEB, JOY KNOPF, CRAIG NICHOLSON, RONALD RABINOWITZ,
AND
ERDAL ERTURK
ABSTRACT Secondary polycythemia is a condition that causes an increase in red blood cell count either because of the physiologic response to stress or inappropriate secretion of erythropoietin. We report a case of a secondary polycythemia caused by ureteropelvic junction obstruction that was successfully treated by laparoscopic nephrectomy. UROLOGY 67: 1291.e1–1291.e3, 2006. © 2006 Elsevier Inc.
S
econdary polycythemia is a condition caused by an increase in red blood cell count either because of a physiologic response to stress or an inappropriate secretion of erythropoietin.1,2 The hallmark of a patient with polycythemia is an elevation in absolute red blood cell count, hematocrit (more than 48% in women or 52% in men), or hemoglobin concentration (greater than 16.5 g/dL in women or 18.5 g/dL in men). Secondary polycythemia is most often due to an oxygen-sensitive erythropoietin response to hypoxia.1,3 It can also present as a paraneoplastic response in the presence of an erythropoietin-secreting tumor.4,5 In rare cases, cobalt exposure, dysregulated angiotensin-feedback mechanisms, such as that seen in post-renal transplant patients, and elevated levels of insulin-like growth factor-1, have also been shown to stimulate erythropoiesis and cause secondary polycythemia.2,6,7 We report a rare case of secondary polycythemia caused by massive hydronephrosis from ureteropelvic junction (UPJ) obstruction that was successfully treated with laparoscopic nephrectomy. CASE REPORT A 24-year-old healthy man had hypertension of 145/98 mm Hg during a routine annual examination. The patient’s physical examination was unreFrom the Department of Urology, University of Rochester Medical Center, Rochester, New York Address for correspondence: Ralph Madeb, M.D., Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642. E-mail: Ralph_ [email protected] Submitted: February 11, 2005, accepted (with revisions): December 19, 2005 © 2006 ELSEVIER INC. ALL RIGHTS RESERVED
markable; however, screening laboratory examinations demonstrated an elevated hematocrit of 64%. All other laboratory testing was within normal limits. The patient was referred to a hematologist for his newly diagnosed polycythemia. The patient denied any familial hematologic disorders, did not smoke, or have any sleep disorders. After additional hematologic testing excluded primary polycythemia, rare familial disorders, and polycythemia vera, the patient was sent for computed tomography for workup of secondary causes of polycythemia, including renal diseases or tumors with ectopic erythropoietin production. Computed tomography of the abdomen and pelvis demonstrated a chronic UPJ obstruction with a massively hydronephrotic right kidney bulging into the right lobe of the liver (Fig. 1). The patient was immediately started on serial phlebotomies, allowing his hematocrit to drop to only 52%. The patient was then referred to our department for definitive management of his chronic UPJ obstruction. The patient underwent uncomplicated laparoscopic nephrectomy. The final pathologic examination revealed medullary and cortical atrophy with fibrosis and mild interstitial nephritis consistent with chronic obstruction. Postoperatively, the patient had no complications, and 4 weeks after his surgery his hematocrit was 46% without the need for subsequent phlebotomies. At 8 weeks postoperatively, the patient’s hematocrit had equilibrated at 41% without further evidence of secondary polycythemia. COMMENT Polycythemia is a blood disorder characterized by an increase in the number of red blood cells in 0090-4295/06/$32.00 doi:10.1016/j.urology.2005.12.042 1291.e1
FIGURE 1. Computed tomography scan demonstrating massively hydronephrotic right kidney bulging into right lobe of liver.
the circulation.1,2 It includes a wide variety of disorders and can be categorized as either primary or secondary. Primary polycythemia is caused by myeloproliferative disorders (eg, polycythemia vera) or by rare familial genetic disorders1,2,8 Secondary polycythemia develops in response to a known hypoxic stimulus or abnormal production of erythropoietin. Erythropoietin is the main hormone regulating red blood cell production, and its serum level increases exponentially in response to anemia or other hypoxic stimuli.1,2,9 Although certain pathologic states may also result in increased erythropoietin, hypoxia is the only physiologic stimulus known to cause an increase in erythropoietin levels.9 Adaptation to hypoxia is critical for survival, and hypoxia sensing provides the impetus for various mechanisms ensuring maintenance of oxygen homeostasis. The activation of the hypoxia sensing mechanisms results in the subsequent activation of an array of genes, including those implicated in glucose metabolism, vasculogenesis, iron transport, and erythropoiesis. Polycythemia has been reported in association with kidney lesions such as Wilms’ tumor (adult and children), polycystic kidneys, and in lesions associated with the von Hippel-Lindau syndrome (renal cell carcinoma, renal hemangioma, pheochromocytoma).10 It has also been reported as a frequent complication after kidney transplantation, an entity known as post-transplant erythrocytosis, which occurs in up to 20% of renal transplant recipients.11 Secondary polycythemia has also been described as a paraneoplastic syndrome in renal cell carcinoma.4,5,12 This is believed to occur owing to increased production of erythropoietin either directly by the tumor or by the adjacent nor1291.e2
mal parenchyma in response to the hypoxia induced by tumor growth. Rarely, hydronephrosis and postrenal obstruction have been reported as the cause of secondary polycythemia.4,5,12–14 Although the overall incidence of erythrocytosis in patients with renal pathologic findings has not been defined, it has been reported as a paraneoplastic syndrome in 1% to 5% of patients with renal cell carcinoma, and approximately 4% of patients with erythrocytosis have renal cell carcinoma,4,12,15 especially those with large tumors. Patients with renal cell carcinoma and erythrocytosis do not necessarily have an elevated serum erythropoietin concentration. However, in patients without other causes of erythrocytosis, successful surgical removal of the renal pathologic features results in resolution of the polycythemia.13,14 Thus, to favorably affect the clinical outcome, it is important to precisely define the causes of polycythemia for each patient and treat them appropriately. To elucidate its cause, it is crucial that all patients who exhibit polycythemia undergo appropriate imaging to look for a curable cause of this disorder. Careful examination of the kidneys is mandatory to detect renal lesions that may be responsible for the polycythemia, such as was the case with our patient. Abdominal imaging by ultrasonography or computed tomography can detect the presence of underlying liver or renal pathologic features. In this instance, a large and rare renal abnormality was disclosed during the appropriate workup for an unknown cause of erythrocytosis. We believe that the chronic UPJ obstruction in our patient caused severe hydronephrosis with a resulting increase in erythropoietin secondary to local renal ischemia. In addition, the severe hydronephrosis with displacement of the kidney may have also contributed to the renal ischemia by encroaching on and displacing the branches of the renal artery. By relieving the obstruction with laparoscopic nephrectomy, the stimulus for erythropoietin production was removed, thus allowing the patient’s hematocrit to settle in the normal range without the need for additional invasive and morbid phlebotomies. Although cases of polycythemia caused by UPJ obstruction have been previously reported, and improvement after open nephrectomy has been described,12–15 this is the first account of definitive treatment of secondary polycythemia with laparoscopic nephrectomy. Moreover, this case has demonstrated that no difference results in the clinical outcome, regardless of the manner in which the etiology is removed—whether by the open or laparoscopic approach. Rather, it is the accurate diagnosis and timely management that most affects patient outcome. UROLOGY 67 (6), 2006
CONCLUSIONS Secondary polycythemia due to chronic UPJ obstruction, although rare, can occur and can be cured by the less-invasive approach of laparoscopic nephrectomy. REFERENCES 1. Berlin NI: Diagnosis and classification of the polycythemias. Semin Hematol 12: 339 –351, 1975. 2. Prchal JT: Classification and molecular biology of polycythemias (erythrocytoses) and thrombocytosis. Hematol Oncol Clin North Am 17: 1151–1158, 2003. 3. Jelinek J, and Prchal JT: Oxygen-dependent regulation of erythropoiesis. Methods Enzymol 381: 201–210, 2004. 4. Gross AJ, Wolff M, Fandrey J, et al: Prevalence of paraneoplastic erythropoietin production by renal cell carcinomas. Clin Invest 72: 337–340, 1994. 5. Mirand EA, Murphy GP, Steeves RA, et al: Extra-renal production of erythropoietin in man. Acta Haematol 39: 359 – 365, 1968. 6. Gregg XT, Reddy V, and Prchal JT: Copper deficiency masquerading as myelodysplastic syndrome. Blood 100: 1493– 1495, 2002. 7. Mok H, Jelinek J, Pai S, et al: Disruption of ferroprotein 1 regulation causes dynamic alterations in iron homeosta-
UROLOGY 67 (6), 2006
sis and erythropoiesis in polycythaemia mice. Development 131: 1859 –1868, 2004. 8. Gordeuk VR, Stockton DW, and Prchal JT: Congenital polycythemias/erythrocytoses. Haematologica 90: 109 –116, 2005. 9. Prchal JT, and Pastore YD: Erythropoietin and erythropoiesis: polycythemias due to disruption of oxygen homeostasis. Hematol J 5(suppl 3): S110 –S113, 2004. 10. Pastore Y, Jedlickova K, Guan Y, et al: Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. Am J Hum Genet 73: 412– 419, 2003. 11. Hilbrands LB, Hoitsma AJ, and Koene RA: Post-transplant haemoglobin levels and host kidney status. Transpl Int 5(suppl 1): S73–S74, 1992. 12. Murphy GP, Mirand EA, Johnston GS, et al: Erythropoietin alterations in human genitourinary disease states: correlation with experimental observations. J Urol 99: 802– 810, 1968. 13. Bailey RR, Shand BI, and Walker RJ: Reversible erythrocytosis in a patient with a hydronephrotic horseshoe kidney. Nephron 70: 104 –105, 1995. 14. Narayana AS, Gallagher F, Kelly DG, et al: Hydronephrosis and polycythaemia. Br J Urol 48: 175–176, 1976. 15. Novick AC, and Campbell SC: Renal tumors, in Walsh PC, Retik AB, Vaughan ED, et al (Eds): Campbell’s Urology, 8th ed. Philadelphia, WB Saunders, 2002, vol 4, pp 2672–2731.
1291.e3