The Congenital and Acquired Solitary Kidney

Management Update

MANAGEMENT UPDATE The Congenital and Acquired Solitary Kidney Ellen Shapiro, MD, FACS, FAAP,* David A. Goldfarb, MD,† Michael L. Ritchey, MD‡ *Department of Urology, New York University School of Medicine, New York, NY; † Urological Institute, Cleveland Clinic Foundation, Cleveland, OH; ‡ Division of Urology, University of Texas, Houston, TX The embryonic insult that results in unilateral renal agenesis may involve not only the ureteral bud but also other mesonephric duct derivatives, including the seminal vesicles, vas deferens, and epididymis; in the female with a solitary kidney, müllerian duct anomalies frequently occur. Normal renal development depends upon a normal ureteral bud, which undergoes orderly branching and penetrates the metanephric blastema at about the fifth week of gestation. Ureteral and kidney development are thought to be interdependent, and when there is failure of the ureteral bud to form or absence of the nephrogenic ridge, the kidney does not develop normally. Unilateral renal agenesis is compatible with normal longevity and does not predispose the contralateral kidney to greater-than-normal risk; nevertheless, patients should have annual surveillance, including a blood pressure measurement, serum creatinine if not initially normal, and urinalysis to detect proteinuria. Removal of one kidney leads to structural and functional changes by the remaining kidney, including increased filtration of the remaining glomeruli. These functional changes have generally been considered beneficial because they mitigate the reduction in the total glomerular filtration rate that would otherwise occur, but experimental evidence suggests that these changes may have an adverse effect on the remaining kidney. Clinical evidence shows that these changes do not lead to renal deterioration in kidney donors because the renal function of kidney donors is well preserved in over 20 years of follow-up after donor nephrectomy. [Rev Urol. 2003;5(1):2–8] © 2003 MedReviews, LLC Key words: Unilateral renal agenesis • Nephrectomy • Acquired solitary kidney • Kidney donor • Hypertension ormal renal development depends upon a normal ureteral bud, which undergoes orderly branching and penetrates the metanephric blastema at about the fifth week of gestation.1 Induction of ureteral bud branching depends on the presence of a normal metanephric blastema.2 When there is failure of the ureteral bud to form or absence of the nephrogenic ridge, the kidney does not develop normally. Ureter development and kidney development are N 2 VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY Congenital and Acquired Solitary Kidney thought to be interdependent. Autopsy studies reveal that renal agenesis can occur with the development of either a partial or a completely normal lead to URA and abnormal mesonephric duct development. The specific timing of this insult affects the crossover of the müllerian ducts Ureter development and kidney development are thought to be interdependent. ureter, and a rudimentary kidney can be present in some cases where there is no identifiable ureter.3 The embryonic insult that results in unilateral renal agenesis (URA) may involve not only the ureteral bud but also other mesonephric duct derivatives, including the seminal vesicles, vas deferens, and epididymis.4,5 In the female, the müllerian duct derivative is dependent upon the normal development of the mesonephric duct; therefore müllerian duct anomalies occur frequently in URA.6 An embryological classification has been proposed based upon the timing of the insult (Figure 1).7 Type I anomalies occur before the fourth week; there is absence of the mesonephric and müllerian duct derivatives, resulting in a solitary kidney and unicornate uterus (Figure 1A). Type II anomalies occur early in the fourth week and and their subsequent fusion (Figure 1B). These patients have a solitary kidney and a didelphic uterus with obstruction of the ipsilateral horn and vagina. Type III anomalies occur after the fourth week and result in only URA. Incidence The incidence of URA is unknown because it is usually asymptomatic. Autopsy studies report an occurrence of about 1 in 1000.8 The incidence of Associated Anomalies The ipsilateral ureter is absent in 50% of cases, and contralateral vesicoureteral reflux is found in about 30%.3,10,11 There can be varying degrees of hydronephrosis and hydroureteronephrosis in the solitary kidney.10,11 URA is commonly associated with genital anomalies, which are 3–4 times more frequent in females than in males.12 In both sexes the gonads are usually normal, but the structures that derive from the wolffian and müllerian ducts can be anomalous.1 Uterine anomalies occur in 1 in over 500 females, and 43% of those have URA12; 30% with URA have reproductive tract anomalies.6 These patients have a solitary kidney and a didelphic uterus with obstruction of the ipsilateral horn and vagina. symptomatic URA is about 1 in 1500.4 The male-to-female ratio is 1.8 to 1, and it occurs more frequently on the left.1,4 With the advent of prenatal MALDEVELOPED MESONEPHRIC DUCT MALDEVELOPED NEPHROGENIC CORD DISPLACED RIGHT MÜLLERIAN DUCT SINOVAGINAL NODE UTERUS UNICORNIS A screening, it has been found that multicystic dysplastic kidneys (MCDK) involute before birth. These may account for some of the cases that were previously thought to be URA.9 UTERUS DIDELPHYS The most common female reproductive tract anomalies include a true unicornate uterus, with complete absence of the ipsilateral horn and Figure 1. Type I anomalies occur before the fourth week and result in a solitary kidney and unicornate uterus. Type II anomalies occur early in the fourth week and result in a solitary kidney and a didelphys uterus with obstruction of the ipsilateral horn and vagina. (A) Solitary kidney and unicornate uterus. (B) Solitary kidney and didelphys uterus with obstruction of the ipsilateral horn and vagina. Reproduced from Magee MC, Lucey DT, Fried FA. A new embryologic classification for uro-gynecologic malformations: the syndromes of mesonephric duct induced mullerian deformities. J Urol. 1979;121:265–267, with permission of the publisher. B VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY 3 Congenital and Acquired Solitary Kidney continued fallopian tube, and a bicornate uterus with rudimentary development of the horn on the affected side.13 An obstructed hemivagina and uterus didelphys (double uterus due to incomplete midline fusion of müllerian ducts) are also often present. Because clinical presentation includes lower abdominal pain or a pelvic mass in a pubertal female, the diagnosis of hematometrocolpos is usually not considered.14–16 URA can be associated with the Mayer-Rokitansky-Küster-Hauser syndrome, in which there is congenital absence of the uterus and vagina.17 has a different embryological origin, it is absent in only 10% of cases.3 Radiologic Evaluation Prenatal sonography has increasingly identified fetuses with URA.1 Compensatory renal growth has been documented in human fetuses with a solitary functioning kidney.21 When the vas or body or tail the epididymis is not palpable or an anomalous vagina or uterus is diagnosed, renal sonography is indicated.1 Sonography reveals a characteristic flattening of the adrenal gland when the kidney is absent.22 A plain film of the abdomen The structures that derive from the wolffian and müllerian ducts can be anomalous. Typically, there are bilateral symmetrical rudimentary uterine anlagen and complete absence of the vagina, with normal fallopian tubes and ovaries. In the atypical form, there are asymmetric uterine remnants, abnormal fallopian tubes, and cystic or anomalous ovaries. The ovarian and renal anomalies are almost always associated with the atypical form.18 In males, anomalies of reproductive organs occur in only 20% of patients with URA.4,6 These include absence or atresia of the seminal vesicles, vas deferens, and epididymis.19 When the vas has been found to be absent in adult males, 79% were found to have an absent ipsilateral kidney.5 The testes are usually uninvolved, and cryptorchism is rare.1 Anomalies of other organ systems can be associated with URA, including those of the cardiovascular system (30%) and musculoskeletal system (14%).8 Unilateral renal agenesis is found in 30% of patients with the vertebral, imperforate anus, tracheoesophageal, and renal (VATER) syndrome.20 Because the adrenal gland 4 VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY may demonstrate a more medial position of the splenic and hepatic flexures, suggesting true URA, whereas the bowel position is normal when there has been involution of a MCDK simulating the appearance of URA.23,24 If URA is diagnosed prenatally, a pelvic sonogram should be performed. If a uterine anomaly is suspected, magnetic resonance imaging is the best modality to delineate the anatomy of the reproductive tract.25 URA is confirmed on technetium 99m–dimercapto succinic acid(99 number of glomeruli as a normal kidney.26 Argueso and colleagues reported on the late effects of congenital URA, including proteinuria (19%), hypertension (47%), and mild renal insufficiency (13%), in middleaged patients.27 Overall survival was not affected by URA. URA is compatible with normal longevity and does not predispose the contralateral kidney to greater-than-normal risk. Rugui and coworkers studied a small group of patients with URA and found an increased incidence of hypertension, hyperuricemia, and decreased renal function but no proteinuria.28 Ritchey reviewed 155 patients ages 2–84 years with URA, with mean follow-up of 44 years. Most (79%) had a normal serum creatinine. Only 5 patients had an abnormal elevation in creatinine (above 2.0 mg/dL). Significant proteinuria (2+ or greater) was found in only 8%, and hypertension occurred in 21%.29 In the long term, patients should have annual surveillance, including a blood pressure measurement, serum creatinine (if not initially normal), and urinalysis to detect proteinuria. Dietary Precautions There is still controversy about the role of protein restriction for patients with a solitary kidney, especially in Compensatory renal growth has been documented in human fetuses with solitary or functioning solitary kidneys. mTc–DMSA) scanning.1 A voiding cystourethrogram is indicated, because there is a high incidence of vesicoureteral reflux.10 Long-Term Prognosis A recent study has shown that the solitary kidney is not hypertrophic but hyperplastic and has twice the children. Brenner and colleagues reported that excess dietary protein is deleterious to the kidney when there is chronic renal failure.30 Several investigators have shown that dietary restriction may slow the rate of progression of renal deterioration.31-33 Although it is reasonable to restrict protein intake in adults with a crea- Congenital and Acquired Solitary Kidney tinine clearance less than 50% of normal, protein restriction in children may lead to malnutrition. The appropriate protein intake for children with chronic insufficiency has not been determined. Children with a creatinine clearance of less than 50% of normal may safely limit protein intake to the recommended daily allowance of protein for children.34 Sports Participation Renal injuries in children are second only to head injuries in frequency,35 and 10% of renal injuries occur in congenitally malformed kidneys.35 Blunt injuries occur in 60%–90% of patients, and only a renal contusion occurs in most cases.36 In the past, the American Medical Association recommended disqualification of athletes with renal disease or solitary kidneys from collision or contact sports.37,38 Recently, people with disabilities have won the right to participate in contact sports, citing the Federal Rehabilitation Act of 1973, and athletes who had previously been disqualified from participation in some sports are now able to compete.37 In 2001, the American Academy of Pediatrics (AAP) published an updated statement on medical conditions affecting sports participation.39 The AAP classifies sports by their degree of contact and collision. The AAP does not recommend participation in boxing and suggests only a limited amount of body checking for hockey players of 15 years and younger. Individuals with one kidney need individual assessment for contact/collision and limited-contact sports. Protective equipment such as “flakjackets" may make limited-contact/ impact sports safe.37,38 Sports with high contact/collision potential are boxing, basketball, diving, field hockey, football (tackle), ice hockey, lacrosse, martial arts, rodeo, rugby, ski jumping, soccer, team handball, water polo, and wrestling. This does not mean that some of the limitedcontact sports, such as downhill skiing and gymnastics, cannot be as dangerous as high-contact or collision sports.39 The Acquired Solitary Kidney Renal Function Following Nephrectomy in Children The removal of one kidney leads to structural and functional changes in the remaining kidney. One of the major functional changes is increased filtration of the remaining glomeruli.40 These functional changes have generally been considered beneficial because they mitigate the reduction in the total glomerular filtration rate (GFR) that would otherwise occur after nephrectomy. However, experimental evidence suggests that these function- failure following subtotal renal ablation is focal glomerulosclerosis. Only three children have been reported to have developed focal segmental glomerulosclerosis many years after completion of treatment for Wilms’ tumor.44,45 The only patient to develop renal failure also had renal artery stenosis of the solitary kidney and had received abdominal irradiation.45 Only limited data exist assessing long-term renal function in children who have undergone nephrectomy and have only a solitary functioning kidney. Argueso and colleagues reported that children with acquired solitary kidneys followed for a mean of 25 years were at increased risk of proteinuria and renal insufficiency, although none had developed end-stage renal disease.46 Few studies have assessed long-term renal func- Most experimental studies involve a loss of over three quarters of the total renal mass, although one study noted abnormalities after removal of only one kidney. al alterations may have an adverse effect on the remaining kidney. Laboratory studies in animals have shown that a marked reduction in renal mass leads to progressive sclerosis of the remaining glomeruli, resulting in proteinuria, hypertension, and progressive azotemia. Most experimental studies involve a loss of over three quarters of the total renal mass, although one study noted abnormalities after removal of only one kidney.41 Most of the experimental studies of hyperfiltration-induced injury have been performed in rats, and it is unclear if these findings are applicable to humans.42,43 The data in humans regarding renal damage from hyperfiltration following nephrectomy are less clear. The renal lesion that occurs in animals and that progresses to renal tion in children following nephrectomy. The abnormalities identified include microalbuminuria, proteinuria, and a reduced GFR.47-50 However, other investigators have found no significant alterations in renal function.51–53 Levitt and colleagues evaluated 53 patients at a mean of 13 years after treatment for Wilms’ tumor.47 Ten patients (19%) were found to have a decreased GFR (< 80 mL/min/1.73m2), 6 (11%) had hypertension, and 5 (9%) had increased urinary excretion of albumin. None of the patients had developed renal failure. Forty of the 53 patients had received radiation (300–1720 cGy) to the remaining kidney. Factors found to be associated with renal dysfunction were age of under 24 months and radiation doses greater than 1200 cGy to the remaining kidney. All 6 patients with radia- VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY 5 Congenital and Acquired Solitary Kidney continued tion nephritis as the etiology for renal failure in this review received radiation doses exceeding 1200 cGy to the remaining kidney. Another report of 27 patients with Wilms’ tumor noted that 33% had a creatinine clearance of under 55mL/min/1.73m2 but did not state whether any of these patients had proteinuria or other clinical manifestations of renal insufficiency.48 Baudoin and colleagues reported on 111 patients, 14 with Wilms’ tumor, who underwent nephrectomy in childhood and were followed for up to 50 years.49 They found that renal function was well maintained at 75% of the reported normal twokidney value. After an interval of more than 25 years postnephrectomy, there was a tendency for a gradual increase in urinary protein and albumin excretion and decrease in GFR. However, there were only 3 patients with a GFR below 60/mL/min/1.73m2. Robitaille and colleagues evaluated 27 patients (4 had Wilms’ tumor) for a mean of 23.3 years after nephrectomy and found only minimal changes in GFR when compared to controls; none had significant pro- teinuria or hypertension.50 Others have assessed the renal functional reserve capacity after unilateral nephrectomy in childhood.54,55 These studies evaluate the function of the solitary kidney after oral protein loading. The report by Regazzoni and colleagues54 found that renal reserve capacity was normal in the first decade after nephrectomy but decreased by 50% by 10–20 years later and 66% by 20–30 years later. Investigators with the National Wilms’ Tumor Study Group (NWTSG) have retrospectively reviewed the incidence of renal failure following treatment for Wilms’ tumor.56 Individuals with bilateral tumors had a much higher incidence of renal failure. In patients undergoing nephrectomy for unilateral tumor, they found an incidence of less than 0.26% of 5368 patients reported to NWTSG studies 1–4. Two thirds of the patients with renal failure after unilateral nephrectomy had Denys-Drash syndrome–associated nephropathy.56 There were few patients with late onset of progressive renal failure suggestive of hyperfiltration-induced injury. A more recent paper from the NWTSG identified an increased risk of renal failure in patients with Wilms’ tumor and aniridia (WAGR) or genitourinary anomalies who had undergone unilateral nephrectomy.57 The cumulative risks of renal failure at 20 years from diagnosis were 38% and 11%, respectively. Of great interest was that the median age at the time of renal failure in the WAGR syndrome was 14.2 years. All cases of renal failure in males with genitourinary anomalies occurred after puberty. These investigators postulated that the late onset of renal failure in patients with genitourinary anomalies and the WAGR syndrome was due to mutation in the WT1 gene. Patients with the Denys-Drash syndrome usually have a germline mutation of WT1. It has been suggested that the severe nephropathy and genital abnormalities in these patients are due to the action of the altered WT1. This study suggests a gradation of phenotypes associated with WT1 mutations. It starts with patients having genitourinary anomalies and a moderate long-term risk of renal Main Points • Autopsy studies reveal that renal agenesis can occur with the development of either a partial or a completely normal ureter, and a rudimentary kidney can be present in some cases where there is no identifiable ureter. • The embryonic insult that results in unilateral renal agenesis (URA) may involve not only the ureteral bud but also other mesonephric duct derivatives, including the seminal vesicles, vas deferens, and epididymis. • The most common female reproductive tract anomalies include a true unicornate uterus, with complete absence of the ipsilateral horn and fallopian tube, and a bicornate uterus with rudimentary development of the horn on the affected side. • Anomalies of other organ systems can be associated with URA, including those of the cardiovascular system (30%) and musculoskeletal system (14%). • The removal of one kidney leads to structural and functional changes in the remaining kidney, including increased filtration of the remaining glomeruli. • Studies of long-term renal function in children following nephrectomy have found abnormalities including microalbuminuria, proteinuria, and a reduced glomerular filtration rate; however, other investigators have found no significant alterations in renal function. • There is no basis to expect renal deterioration in kidney donors because renal function is well preserved in over 20 years of follow-up after donor nephrectomy. 6 VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY Congenital and Acquired Solitary Kidney failure, progresses to WAGR patients who have more severe genitourinary anomalies and high long-term risk of renal failure, and finishes with the Denys-Drash syndrome patients, who have markedly distorted genitourinary development and a high risk of early renal failure. In summary, it is important that these children who have a solitary functioning kidney have long-term follow-up with measurements of blood pressure, urine protein, serum creatinine, renal clearance, and renal size. These children should be followed until they reach adulthood because they could experience subtle renal deterioration at that time or later in adult life. Renal Function Following Donor Nephrectomy Renal outcomes in adults with acquired solitary kidney can be studied in a group of patients undergoing donor nephrectomy. Published reports in these patients show no progressive renal injury up to 20 years after kidney donation.58 The Cleveland Clinic Foundation recently reported on the impact of donor nephrectomy on estimates of GFR, urinary protein excretion, and the development of hypertension.59 Of the 70 patients followed, representing approximately 39% of the live donor pool between 1963–1975, the mean patient followup was 25 years. The average donor age at follow-up was 64 years (range 39–84 years). There was a 72% reduction in the value of the 24-hour urinary creatinine clearance which was not dependent upon age. Serum creatinine and systolic blood pressure were significantly increased, although the values were still within the normal range (less than 140/90 mm Hg). Serum creatinine was higher in males before and after donation, but there were no gender differences in the 24-hour urinary creatinine clearance. There were no differences in these values based on the age at donation. Values for 24-hour urine creatinine clearance after donation were higher than the expected single GFR for males, and no difference was found for females. The 24-hour urine protein and albumin excretion after donation were higher in males compared with females after donation, but no differences in values were found based on the age at donation. Proteinuria developed in 13 (19%) and albuminuria developed in 23 of 63 patients (36%). No correlation was found between proteinuria and renal function. There was a correlation between albuminuria and serum creatinine but not creatinine clearance. When the group of patients who developed proteinuria was further evaluated, most were found to have mild proteinuria (less than 0.8 g/24 hr.) but 5 had more significant proteinuria. These patients were also noted to have a median proteinuria value before donation of 0.21 g/24 hr, which was higher than the remainder of the group in the study population. These patients represent a subset population who would be at risk for the development of long-term significant proteinuria following donor nephrectomy. No donor was hypertensive (blood pressure 140/90 mm Hg or greater or normotensive but managed with antihypertensive medications) at the time of donation. Postoperatively, 31 (48%) were hypertensive, which is comparable to the 54% noted in the National Health and Nutrition Examination Survey for Adults 65–74 years of age.60 Although systolic blood pressure increased significantly after donation but was still within the normal range (140 mm Hg or less), there was no change in the diastolic blood pressure. Systolic blood pressure after donation increased in all patients but was higher and in the hypertensive range in donors over 50 years of age. This is due to the age-related increase in blood pressure observed in the general population. One patient developed glomerulonephritis without long-term renal sequelae. End-stage renal disease developed in two patients, but there was insufficient information to determine its etiology. The authors conclude that there is no basis to expect renal deterioration in kidney donors because renal function is well preserved in over 20 years of followup after donor nephrectomy. References 1. Bauer SB. Anomalies of the kidney and ureteropelvic junction. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, eds. Campbell’s Urology, II, 7th ed. Philadelphia, PA: WB Saunders Company; 1998:1708–1755. 2. Davidson WM, Ross GIM. Bilateral absence of the kidneys and related congenital anomalies. J Pathol Bacteriol. 1954;68:459. 3. Ashley DJB, Mostofi FK. Renal agenesis and dysgenesis. J Urol. 1960;83:211. 4. Doroshow LW, Abeshouse BS. Congenital unilateral solitary kidney: report of 37 cases and a review of the literature. Urol Surv. 1961;11:219. 5. Donohue RE, Fauver HE. Unilateral absence of the vas deferens. JAMA. 1989;261:1180. 6. Thompson DP, Lynn HB. Genital anomalies associated with solitary kidney. Mayo Clin Proc. 1966;41:538. 7. Magee MC, Lucey DT, Fried FA. A new embryologic classification for uro-gynecologic malformations: the syndromes of mesonephric duct induced müllerian deformities. J Urol. 1979;121:265. 8. Emanuel B, Nachman RP, Aronson N, Weiss H. Congenital solitary kidney: A review of 74 cases. Am J Dis Child. 1974;127:17. 9. Mesrobian H-G, Rushton HG, Bulas D. Unilateral renal agenesis may result from in utero regression of multicystic renal dysplasia. J Urol. 1993;150:793. 10. Atiyeh B, Hussmann D, Baum M. Contralateral renal anomalies in patients with renal agenesis and noncystic renal dysplasia. Pediatrics. 1993;91:812. 11. Cascio S, Paran S, Puri P. Associated urological anomalies in children with unilateral renal agenesis. J Urol. 1999;162:1081–1083. 12. Semmens JP. Congenital anomalies of the female genital tract: functional classification based on review of 56 personal cases and 500 reported cases. Obstet Gynecol. 1962;19:328. 13. Shumaker HB. Congenital anomalies of the genitalia associated with renal agenesis. Arch Surg. 1938;37:586. 14. Stassart JP, Nagel TC, Prem KA, et al. Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience. Fertil Steril. 1992;57:756. 15. Yoder IC, Pfister RC. Unilateral hematocolpos and ipsilateral renal agenesis: report of two cases and review of the literature. AJR Am J Roentgenol. 1976;127:303. VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY 7 Congenital and Acquired Solitary Kidney continued 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 8 Gilliland B, Dick F. Uterus didelphys associated with unilateral imperforate vagina. Obstet Gynecol. 1976;48(suppl 1):5S. Tarry WF, Duckett JW, Stephens FD. The Mayer-Rokitansky syndrome: pathogenesis, classification and management. J Urol. 1986;136:648. Strubbe EH, Willemsen WNP, Lemmens JAM, et al. Mayer-Rokitansky-Küster-Hauser syndrome: distinction between two forms based on excretory urographic, sonographic, and laparoscopic findings. AJR Am J Roentgenol. 1992;160:331. Ochsner MG, Brannan W, Goodier EH. Absent vas deferens associated with renal agenesis. JAMA. 1972;222:1055. Barry JE, Auldist AW. The VATER association. Am J Dis Child. 1974;128:769. Mandell J, Peters CA, Estroff JA, et al. Human fetal compensatory renal growth. J Urol. 1993;150(2 pt 2):790–792. Hoffman CK, Filly RA, Callen PW. The “lying down" adrenal sign: A sonographic indicator of renal agenesis or ectopia in fetuses and neonates. J Ultrasound Med. 1992;11:533. Curtis JA, Sadhu V, Steiner RM. Malposition of the colon in right renal agenesis, ectopia and anterior nephrectomy. AJR Am J Roentgenol. 1977;129:845. Mascatello V, Lebowitz RL. Malposition of the colon in left renal agenesis and ectopia. Radiology. 1976;120:371. Tanaka YOU, Kurosaki Y, Kobayashi T, et al. Uterus didelphys associated with obstructed hemivagina and ipsilateral renal agenesis: MR findings in seven cases. Abdom Imaging. 1998;23:437. Maluf NS. On the enlargement of the normal congenitally solitary kidney. Br J Urol. 1997;79:836–841. Argueso LR, Ritchey ML, Boyle ET Jr, et al. Prognosis of patients with unilateral renal agenesis. Pediatr Nephrol. 1992;6:412. Rugui C, Oldrizzi L, Lupo A, et al. Clinical features of patients with solitary kidneys. Nephron. 1986;43:10. Ritchey ML. Prognosis of the solitary kidney. In: Kramer SA, ed. Problems in Urology. Philadelphia, PA: JB Lippincott Company; 1990:595–605. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease. N Engl J Med. 1982;307:652–659. Ihle BU, Becker GJ, Whitworth JD. The effects of protein restriction on the progression VOL. 5 NO. 1 2003 REVIEWS IN UROLOGY 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. of renal insufficiency. N Engl J Med. 1989;321:1773–1777. Oldrizzi L, Rugiu C, Valvo E, et al. Progression of renal failure in patients with renal disease of diverse etiology on protein-restricted diet. Kidney Int. 1985;27:553–557. Walser M, Mitch W. Collier V. The effect of nutritional therapy on the course of chronic renal failure. Clin Nephrol. 1979;11:66–70. Rink RC, Adams MC. The solitary kidney. In: Health and Disease, AUA Update Series 11; 1992:lesson 35. Morse, TS. Renal injuries. Pediatr Clin North Am. 1975;22:379. Sagalowsky AI, Peters PC. Genitourinary trauma. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, eds. Campbell’s Urology, II, 7th ed. Philadelphia, PA: WB Saunders Company; 1998:3085–3118. Wichmann S, Martin DR. Single-organ patients: balancing sports with safety. Phys Sportsmed. 1992;20:176–182. Dorsen PJ. Should athletes with one eye, kidney, or testicle play contact sports? Phys Sportsmed. 1986;14:130–138. Committee on Sports Medicine and Fitness. American Academy of Pediatrics: medical conditions affecting sports participation (RE0046). Pediatrics. 2001;107:1205–1209. Anderson S, Meyer TW, Brenner BM. The role of hemodynamic factors in the initiation and progression of renal disease. J Urol. 1985;133:363–368. Shimamura T, Morrison AB. A progressive glomerulosclerosis occurring in partial fivesixths nephrectomized rats. Am J Pathol. 1975;79:95–101. Provoost AP, DeKeijzer MH, Molenaar JC. Effect of protein intake on lifelong changes in renal function of rats unilaterally nephrectomized at young age. J Lab Clin Med. 1989;114:19–26. Provoost AP, Baudoin P, DeKeijzer MH, et al. The role of nephron loss in the progression of renal failure: experimental evidence. Am J Kidney Dis. 1991;17:27–32. Scully RE, Mark EJ, McNeely BU. Case records of the Massachusetts General Hospital (case 171985). N Engl J Med. 1985;312:1111–1119. Welch TR, McAdams AJ. Focal glomerulosclerosis as a late sequela of Wilms’ tumor. J Pediatr. 1986;108:105–109. Argueso LR, Ritchey ML, Boyle ET Jr, et al. Prognosis of the solitary kidney after unilateral nephrectomy in childhood. J Urol. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 1992;148:747–751. Levitt GA, Yeomans E, Dicks Mireaux C, et al. Renal size and function after cure of Wilms’ tumor. Br J Cancer. 1992;66:877–882. Bertolone SJ, Patel CC, Harrison HL, Williams G. Long term renal function in patients with Wilms’ tumor [abstract]. Proc Am Soc Clin Oncol. 1987;6:265. Baudoin P, Provoost AP, Molenaar JC. Renal function up to 50 years after unilateral nephrectomy in childhood. Am J Kidney Dis. 1993;21:603–611. Robitaille P, Mongeau JG, Lortie L, Sinnassamy P. Long-term follow-up of patients who underwent nephrectomy in childhood. Lancet. 1985;1:1297–1299. de Toledo JS, Galindo JR, Melcon GC, et al. Renal function in long-term survivor of Wilms’ tumor. Med Pediatr Oncol. 1995;25:265. Barrera M, Roy LP, Stevens M. Long-term follow-up after unilateral nephrectomy and radiotherapy for Wilms’ tumor. Pediatr Nephrol. 1989;3:430–432. Bhisitkul DM, Morgan ER, Vozar MA, Langman CB. Renal functional reserve in long-term survivors of unilateral Wilms’ tumor. J Pediatr. 1990;118:698–702. Regazzoni BM, Genton N, Pelet J, et al. Longterm followup of renal functional reserve capacity after unilateral nephrectomy in childhood. J Urol. 1998;160:844–848. Donckerwolcke RM, Coppes MJ. Adaptation of renal function after unilateral nephrectomy in children with renal tumors. Pediatr Nephrol. 2001;16:568–574. Ritchey ML, Green DM, Thomas P, et al. Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol. 1996;26:75–80. Breslow NE, Takashima J, Ritchey ML, et al. Renal failure in the Denys-Drash and Wilms’ tumor-aniridia syndromes. Cancer Res. 2000;60:4030–4032. Najarian JS, Chavers BM, McHugh LE, et al. 20 years or more follow-up of living kidney donors. Lancet. 1992;340:807. Goldfarb DA, Matin SF, Braun WE, et al. Renal outcome 25 years after donor nephrectomy. J Urol. 2001;166:2043–2047. Burt VL, Cutler JA, Higgins M, et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the health examination surveys, 1960 to 1991. Hypertension. 1995;26:60.