Renal Papillary Necrosis in a Patient with Sickle Cell Trait GINO ZADEII and JAMES W. LOHR Department of Medicine, State University of New York at Buffalo, Buffalo, New York, and the Veterans Affairs Medical Center, Buffalo, New York. Abstract. A patient with sickle cell trait who presented with abnormalities associated with sickle cell trait is described. The gross hematuria and was subsequently found to have renal management of the primary clinical manifestations of this papillary necrosis is presented. The hematuria resolved with disorder, hematuria and papillary necrosis, are discussed. conservative therapy consisting of bed rest and hydration with (J Am Soc Nephrob 8: 1034-1040, 1997) hypotonie intravenous fluids. The pathophysiology of renal A variety of renal abnormalities have been described in pa- mg/dl. Urine dipstick revealed a specific gravity of I .020, pH tients with sickle hemoglobinopathies (1-5). Most of the liter- 5.5, 3+ blood, 3+ protein, and was negative for glucose, ature has dealt with patients with homozygous sickle cell ketones, and leukocyte esterase. The microscopic exam anemia (HbSS), although the incidence of heterozygous sickle showed many red blood cells (RBC), but no RBC casts or cell trait in the United States has been estimated to be 40 times white blood cells were seen. Urine culture showed no growth. as great (1). The patient was evaluated by a urologist, and an intravenous We report a case of a patient with sickle cell trait presenting pyelogram was performed that showed bilateral papillary ne- with gross hematuria, who was subsequently found to have erosis (Figure 1 ). The patient was placed at bed rest and given papillary necrosis on intravenous pyelography. A discussion of intravenous half-normal saline at a rate of 150 mlIh. The the renal abnormalities associated with sickle cell trait and the hematuria cleared on day 4. Before discharge, he had cystos- approach to management of these disorders is presented. copy that was unremarkable. Retrograde urogram could not be completed due to patient discomfort. Case Report The patient has not had any recurrent hematuria in the 9 mo An African-American man 66 yr of age presented to the since discharge. Buffalo Veterans Affairs Medical Center with a 2-d history of gross hematuria. He denied having experienced fever and Discussion chills, dysuria, or flank pain. He had no history of recent Several renal abnormalities have been described in patients trauma or nephrolithiasis. Past medical history was significant with sickle cell disorders. These vary depending on whether for hypertension, hypereholesterolemia, and benign prostatie the patient has sickle cell disease or sickle cell trait. In sickle hypertrophy, which had been evaluated in the previous year cell disease, there are two abnormal genes related to hemoglo- and found not to be causing any urinary tract obstruction. He bin production, with at least one being the gene for hemoglobin also had sickle cell trait, diagnosed by AS pattern on hemo- S. These include sickle cell anemia, sickle cell-hemoglobin C globin eleetrophoresis in 1986. The patient was taking lisino- disease, sickle cell-thabassemia, and some less common disor- pril and eolestipol. He denied taking any nonsteroidal inflam- ders. Nephropathy associated with sickle cell disease has been matory drugs. well reviewed (1-4). In sickle cell trait, there is a normal gene, The physical examination revealed a well-developed man in along with the gene for hemoglobin S. This is the most corn- no acute distress. Blood pressure was 140/70 mmHg, pulse was mon hernogbobinopathy in the United States, present in more 76 beats/mm, and temperature was 36.5#{176}C. Examination of the than 2 million people. This discussion will be restricted to renal abdomen showed no evidence of hepatosplenomegaby. No cos- findings in sickle cell trait, with only a mention of the con- tovertebral tenderness was noted. The physical examination trasting features of sickle cell anemia. was otherwise unremarkable except for a symmetric, mildly enlarged prostate gland. Laboratory tests showed normal com- Pat hophysiologv plete blood cell counts, clotting studies, and electrolytes. Blood The renal medullary interstitium may achieve an osmolarity urea nitrogen was I 2 mg/dl. and serum ereatinine was I .3 of 800 to 1200 mosmol/kg based on the countercurrent mech- anism, which involves the loops of Henle and the blood supply of the mideortical juxtarnedullary nephrons. The medullary Received March 7. 1996. Accepted October 9. 1996. interstitium is made hypertonic by reabsorption of sodium Correspondence to Dr. James W. Lohr. Department of Medicine ( I 1 1A), Veterans Affairs Medical Center. 3495 Bailey Avenue. Buffalo. NY 14215. chloride without water in the ascending limb of the loop of 1046-6673/0806- l034$03.00/0 Henle. Solute is transferred from the tubular lumen into the Journal of the American Society of Nephrology rnedullary interstitial fluid, raising the osmotic concentration of Copyright 0 1997 by the American Society of Nephrology the interstitial fluid relative to tubular fluid. The hyperosmotie Papillary Necrosis and Sickle Cell Disorders 1035 Figure 1. Intravenous pyelogram showing bilateral papillary necrosis in patient with sickle cell trait. medullary interstitium causes removal of water from the de- to leak into the collecting system. This results in a reduced scending limb of the loop of Henle and raises the osmolality of number of vasa recta and loss of the normal medullary archi- the tubular fluid as it approaches the tip. Urea also contributes tecture as revealed by microangiographic studies (7). to the hyperosmolabity of the medullary interstitium by diffu- Eventually, these events may lead to papillary necrosis. The sion from the inner rnedullary collecting tubule. The vasa recta papillary necrosis usually involves the tip of the papilla, with are vessels with hairpin-like construction that lie near the loops no involvement or destruction of the fornices. Gross pathologic of Henle and carry blood through the medullary tissue at a exam shows one or more papillae with areas of necrosis, much slower rate than cortical vessels. Thus, this blood comes usually involving one-third of the papilla (8). Calcification into contact with the hypertonic medullary interstitial fluid may be seen in old areas of necrosis. Microscopic examination through the capillary wall. reveals total or partial necrosis of tubular and collecting duct In patients with sickle cell trait, the hyperosmolar interstitial epithelium in the area of necrosis. There may be evidence of fluid draws water from the cells, resulting in an increased expansion of the interstitial space with fibrosis. concentration of sickle cell hemoglobin, the most important The functional renal changes (Table 1) that are seen in sickle determining factor for sickling (Figure 2). Another factor that cell trait are primarily due to the loss of vasa recta, which may contribute to red blood cell sickling is the low oxygen disrupts the countercurrent exchange system. This results in an tension present in the medulla. Along with the fact that the impaired ability to concentrate the urine in patients with sickle medulla receives less than 10% of the renal blood flow, the cell trait (9-12). This appears to be reversible early in life, but configuration of the vasa recta capillaries results in a loss of there is a continual gradual decrease throughout life, which oxygen as the blood enters the medulla with subsequent uptake then becomes fixed. In patients over 50 yr of age, maximum by the opposing ascending capillaries leaving the medulla. This urine osmolality generally will not exceed 450 mosmol (9). can result in oxygen tensions of 20 mmHg or less in the The ability to dilute the urine has been found to be normal in medulla, with sickling often occurring at less than 45 mmHg patients with sickle cell trait (12). due to polymerization of sickle cell hemoglobin. This hypoxia, Patients with sickle cell trait have been found to have a along with the acidic rnedullary pH, also promotes sickling of normal ability to excrete acid in response to ammonium chlo- RBC (6). As sickling occurs, there is an increase in blood ride loading ( 10). This is in contrast to those with sickle cell viscosity, which may further slow the blood flow in the rued- disease who frequently have an incomplete distal renal tubular ullary capillaries. acidosis ( 10). Potassium excretion has also been studied and Initiably, capillaries become engorged with erythrocytes. was found to be normal in patients with sickle cell trait, Subsequently, RBC sickling in the vasa recta causes formation whereas it was frequently impaired in those with sickle cell of rnicrothrombi, infarction, and formation of collateral vessels anemia (13.14). Sodium handling is thought to be normal in (7). Capillaries develop increased permeability, allowing RBC patients with sickle cell trait. although this has not been well 1036 Journal of the American Society of Nephrology Renal Medullaiy malities, intravenous pyelogram, and cystoscopy . Hemoglobin electrophoresis should be performed in all patients with hema- tuna of unknown etiology, as sickle cell trait is not exclusively Acidosis Hypertonicity Hypoxia seen in African-American patients (18). Papillary Necrosis. Renal papillary necrosis may occur in sickling of RBC up to 50% of patients with sickle cell trait who present for evaluation (19,20). It is generally discovered during evaluation in vasa recta of hematuria.