Medullary Sponge Kidney Associated with Congenital Hem ihypertrophy

Transcription

1 EDITORIAL COMMITrEE Tomas Berl, Editor William Henrich Mark Paller Fred Silva Denver, CO Toledo, OH Minneapolis, MN Oklahoma City, OK NEPHROLOGY TRAINING PROGRAM: DUKE UNIVERSITY MEDICAL CENTER The nephrology training program at the Duke University School of Medicine provides comprehensive training in clinical nephrology. dialysis, renal transplantation, and hypertension. Fellowship options include a 3-year clinical investigator pathway, a 3-year basic science investigator pathway, and a 2-year clinical training track. Each fellow completes a clinical program that includes rotation on three services: the transplant service, the acute nephrology service, and the consult service at the Durham Veterans Affairs Medical Center. During the transplant rotation, the fellow is involved in the evaluation of donor and recipient candidates for kidney and simultaneous kidney-pancreas transplant. Post-transplant care is primarily the responsibility of the nephrology division. The acute service provides interventional support to Duke University Medical Center s intensive care units. an inpatient renal ward, and a general renal consultation service. Outpatient activities include the longitudinal management of fellows own renal transplant, dialysis, chronic renal failure, and nephrology referral patients. Clinical facilities include the bed Duke University Medical Center and the 450-bed Durham Veterans Affairs Medical Center. The division directs five outpatient dialysis facilities, providing care for over 375 dialysis patients. Active peritoneal and home hemodialysis programs are included. The renal transplant program at Duke University Medical Center averages 70 kidney and simultaneous kidney-pancreas transplants each year. The Duke Hypertension Center provides the opportunity for clinical experience in refractory hypertension. A National Institutes of Health (NIH)- supported General Clinical Research Center is often used by the division. The basic science investigator pathway includes 2 years of research under the direction of a faculty sponsor. The division currently has a NIH-training grant as welt as a Transplantation Program Project Grant with three faculty members involved. NIH-funded basic science investigation is also ongoing in areas including metabolic bone disease, genetic predisposition for hypertension. signal transduction, and receptor regulation. Advanced training in biostatistics. study design. and epidemiology (including the opportunity to pursue a Masters of Health Science degree) is available to fellows choosing the clinical investigator pathway. NIH- and industry-funded trials in hemodialysis vascular access, cardiovascular disease in renal failure patients, adequacy of dialysis and dialysis membranes, use of atrial natriuretic peptide in acute renal failure, and treatment of metabolic bone disease in hemodialysis patients are ongoing. The straight clinical pathway includes 18 months of intensive clinical training that encompasses all areas of nephrotogy. including the management of outpatient hemodialysis and significant outpatient transplant and hypertension experience. with a brief exposure to clinical research. In addition, structured exposures to renal pathology and histocompatibility are available. Medullary Sponge Kidney Associated with Congenital Hem ihypertrophy Olafur Skuli Indridason, Laura Thomas, and Michael Berkoben2 L. Thomas, Department of Radiology, Duke University O.S. Indridason, M. Berkoben, Division ofnephrology, Medical Center, Durham, NC Duke University Medical Center, Durham, NC (J. Am. Soc. Nephrol. 1996; 7: ) ABSTRACT Medullary sponge kidney is a developmental disor Received September 2 Correspondence Accepted to Dr. M. Berkoben, Box February 3014, Duke University Medical Center, der characterized by ectatuc and cystic malformation Durham, NC of the collecting ducts and tubules. Clinical manifes- 104&6673/ $03.OOIO tations include urinary tract infections, renal stones, Journal of the American SocIety of Nephrology.. Copyright 1996 by the American Society of Nephrology and hematuria. It can be associated with other de- Journal of the American Society of Nephrology 1123

2 Medullary Sponge Kidney and Congenital Hemihypertrophy velopmental disorders. A case of medullary sponge kidney associated with congenital hemihypertrophy, complicated by nephrocalcinosis and nephrolithiasis, is reported here. M edullary sponge kidney is characterized by ectatic and cystic malformations of the collecting ducts and tubules of one or more papillae of one or both kidneys. The cysts measure 1 to 7.5 mm in diameter, are most prominent in the Inner paplllae, are lined with cuboidal or columnar epithellum, and communicate with the dilated ducts and tubules (1-3). In and of themselves, these anatomic abnormalities produce no symptoms. The morbidity of this disorder is the result of nephrobithiasis and urinary tract infection, both of which are thought to be secondary to the anatomic abnormalities. Not surprisingly, then, medullary sponge kidney is often diagnosed incidentally by intravenous urography In the work-up of hematuria, kidney stones, or urinary tract infections ( 1 ). Although usually diagnosed In adult life, the disorder is thought to be congenital. It has been described in association with other congenital disorders ( 1,4). We report a case of medullary sponge kidney associated with congenital hemihypertrophy. The case also demonstrates many of the salient dm1- cab features of medublary sponge kidney. Figure 1. Abdominal radiograph done on initial presentation showed extensive nephrocalcinosis. Key Words: Hypercalciuria. kidney calculi. renal tubular acidosis, nephrocalcinosis CASE REPORT The patient is a 35-yr-old man who experienced acute renal colic from a kidney stone in October Initial evaluation was remarkable for hypercalciurla (450 mg/24 h), borderline hyperuricosuria (789 mg/24 h), and a high urinary sodium excretion rate (383 mmol/24 h). He had normal citrate excretion (2.6 mmol/24 h) but mildly elevated oxalate excretion (44.0 mg/24 h) rates. His serum creatinine concentration was 1. 1 mg/dl, BUN 24 mg/dl, sodium 143 mmol/l, potassium 4.2 mmol/l, chloride 103 mmol/l, and CO2 29 mmoh/l. His serum calcium concentration was mg/dl, phosphorus 3.4 mgi dl, uric acid 6.2 mg/dl, and albumin 4.6 g/dl. The serum intact parathyroid hormone bevel was 38 pg/ml (normal range, 13 to 64 pg/ml), the serum 1,25-dlhydroxyvltammn D level was 29 pg/ml (normal range, 15 to 50 pg/ml), and the serum 25-hydroxyvitamin D level was 27 ng/ml (normal range, 15 to 80 ng/ml). The hemogram was normal. Urinalysis showed ph 6.0, specific gravity 1.014, and 19 white blood cells per high-powered field (hpf). An abdominal radiograph demonstrated extensive bilateral nephrocalcinosis (Figure 1 ). Computed tomography of the abdomen demonstrated extensive bilateral nephrocalcinosis and milk of calcium (chalky white liquid) in ectatic renal tubules (Figure 2). A high fluid intake and dietary sodium and oxalate restriction were prescribed. In March 1993, a 24-h urine sample was Figure 2. Computed tomography scan of abdomen demonstrated ectatic tubules and extensive nephrocalcinosis. taken, which contained 367 mg calcium and 205 rnmol sodium. In December 1993, a 24-h urine sample was taken, containing 323 rng calcium and 304 mmol sodium. Urinalysis was remarkable for hematuna and pyuria, but a urine culture yielded no growth. An abdominal radiograph demonstrated progression of nephrocalcinosis. The patient was referred to us for further evaluation and management. At the time ofhis first visit to us in January 1994, he was asymptomatic, was following the prescribed diet, and was maintaining a urine volume greater than 2 L per day. His past medical history was remarkable for surgical repair of an umbilical hernia in and surgery for a discrepancy in leg length in the early 1970s. He had no history ofgout, inflammatory bowel disease, chronic diarrhea, hyperparathyroidism, neck irradiation, or granubomatous disease. His only medication was a multivitamin that included vitamins A (10,000 IU), C (3000 mg), and D (100 IU). He was a vegetarian. He did not drink milk or eat cheese. He took no antacids, calcium supplements, or protein supplements. The family history was significant in that his mother passed a kidney stone shortly after 1124 Volume 7. Number

3 Indridason et al giving birth to him. In addition, the patient reported that one of his mother s arms was much smaller than the other. The physical examination was unremarkable except that the right leg was larger than the left (Figure 3). The circumference of the right thigh was 58.8 cm and that of the left 55.2 cm. The circumference of the right calf was 40.8 cm and that of the left 36.0 cm. Pertinent laboratory data included a serum potassium level of3.8 meq/l, a serum CO2 bevel of 33 meq/l, and a serum creatinine concentration of 1.2 mg/dl. Urinalysis showed a specific gravity of , ph of5.0, 19 white blood cells per hpf, and 3 red blood cells per hpf. A urine culture again yielded no growth. A 24-h urine sample contained 208 mg calcium, 105 mmol sodium, 42 mg oxalate, and 4.4 mmol citrate. It was recommended that the patient discontinue taking the multivitamin. Because of persistent hypercalciuria, a thiazide diuretic was prescribed. He refused to take it. In November 1994, his serum creatine level was 1.0 mg/dl and serum CO2 bevel was 29 meq/l. A 24-h urine sample contained 384 mg calcium, 155 mmob sodium, and 838 mg uric acid. An abdominal radiograph demonstrated no progression of nephrocalcinosis. He has continued to pass minute kidney stones on occasion, but has experienced no renal colic, hematuria, or urinary tract infections. ETIOLOGY The association of medullary sponge kidney with congenital abnormalities and the unchanging nature of the cystic lesions over time suggest that it is a developmental disorder ( 1,4). It Is usually sporadic but has been reported in two or more successive generations of several families (1). PREVALENCE In a geographical area of the United Kingdom with a population of 254,000, Mayall found 1 2 cases of medullary sponge kidney in 2600 intravenous urograms, suggesting a prevalence of 5 per 100,000 in the general population (5). This is likely to be an underestimatlon, as asymptomatic patients do not undergo urography. Other studies have shown a prevalence of 0.5 to 1 % in unselected patients undergoing urography ( 1,6). In patients with stones, the prevalence has been reported to be 2.6 to 2 1 % ( 1,6-8). When cornpared with men with calcium stones, women with calcium stones are more likely to have medullary sponge kidney ( 1,7). The prevalence of medullary sponge kidney may be as high as 25% in women with calcium stones (1). PATHOPHYSIOLOGY The cysts frequently contain calcific deposits. These deposits are radio-opaque, frequently appear in clusters on plain film of the abdomen, and are composed of an admixture of calcium apatite and calcium oxalate or of calcium apatite alone ( 1 ). Erosion of these concretions through the papillary wall into the renal pelvis may head to symptomatic stone disease. Several factors contribute to the formation of intrapapillary calcium concretlons (Table 1 ). First, urinary stasis within the cysts likely plays a role ( 1 ). Second, cellular debris and hyahine material In the cysts may provide a matrix for stone formation ( 1 ). Third, Impaired urinary acidification may decrease the solubility of calcium apatite (9-12). Finally, any or all of the risk factors for idiopathic calcium stone disease (hypercalciuria, hyperoxaburia, hyperuricosuria, hypoci- Figure 3. Views showing enlarged right leg of patient. Journal of the American Society of Nephrology 1125

4 Medullary Sponge Kidney and Congenital Hemihypertrophy TABLE 1. Factors that may promote formation of intrapapillary concretions Urinary Stasis Infection Intraluminal Debris Impaired Urinary Acidification Risk Factors for Calcium Stone Disease (Hypercalciuria, Hyperoxaiuria, Hypocitraturla, Hyperuricosuria) traturia) may be present In patients with medulbary sponge kidney ( 1,6,8). The impaired urinary acidification and the hypercalciurla of medullary sponge kidney merit further comment. Impaired Urinary Acidification The terminal collecting duct is a principal site of the anatomic lesions of medulbary sponge kidney (1,2). The terminal collecting duct also plays a major role In urinary acidification. Indeed, investigators have reported impaired distal acidification in a substantial proportion of patients with medullary sponge kidney. Higashihara and coworkers (9) studied 1 1 stone formers with medullary sponge kidney. Baseline arterial blood ph was normal in all, but the baseline plasma bicarbonate concentration was low In seven patients. The urine ph of four patients did not fall below 5.3 after ammonium chloride loading and thus met the criteria for partial distal renal tubular acidosis. All four had low plasma bicarbonate concentrations. The urine ph of another five patients did not fall below When compared with healthy subjects and to patients with bilateral stones, the 1 1 patients with medullary sponge kidney had lower baseline plasma bicarbonate concentrations (mean, meq/l) and had higher urine ph values in response to ammonium chloride loading. Similarly, Osther and colleagues (10) studied 13 stone formers with medublary sponge kidney and found two with complete and six with partial distal renal tubular acidosis. More recently, Osther et at. ( 13) reported his findings In ten women with medullary sponge kidney. Four had partial renal tubular acidosis. When compared with the six women with normal urinary acidification, the four with partial renal tubular acidosis had lower fasting plasma bicarbonate concentrations (20.5 meq/l versus 23.8 meq/l) and lower 24-h urinary citrate excretion rates (0.93 mmol versus 3.58 mmoh; normal, >1.8 mmol). Other investigators have found that the 24-h urinary citrate excretion rate is bower in recurrent stone formers with medullary sponge kidney than In idiopathic stone formers (11). The results of studies of urinary acidification in meduhlary sponge kidney are summarized In Table 2. On the basis of these results, we believe that we can make the following statements. First, a substantial proportion (perhaps one half) of patients with medulbary sponge kidney have partial or complete distal renal tubular acidosis. Second, a low plasma bicarbonate concentration and hypocitraturia will identify some, but not all, patients with renal tubular acidosis (9, 12, 13). Third, when compared with healthy subjects or to patients with bilateral stones, patients with medullary sponge kidney have lower baseline plasma bicarbonate concentrations and higher minimal urine ph values in response to ammonium chloride loading TABLE 2. Investigations of urinary acidification in medullary sponge kidneya. investigators (Reference Number) Number Mean Number with Baseline of Renal Plasma.. Patients Tubular Bicarbonate (Male/ Acidosis Concentration Female) (Partial/ in Patients with Complete) PTA (meq/l). Citrate Excretion Backman et al. (1 1) 14 (9/5) 3 (3/0) (Not reported) Mean 24-h urinary citrate excretion rate lower in patients with MSK than in idiopathic stone formers Higashihara et al. (9) 11 (4/7) 4 (4/0) 21.8 Not reported Osther et a!. (10) 13 (3/10) 8 (6/2) (Not reported) Not reported Osther et a!. (1 3) 10 (0/ 10) 4 (4/0) 20.5 Mean 24-h urinary citrate excretion rate 0.93 mmol in patients with PTA and 3.58 mmol In those without PTA Mayers et a!. (12) 24 (9/ 15) 12 (5/7) (Not reported) Hypocitraturia in seven of 12 patients with PTA a PTA, renal tubular acidosis; MSK medullary sponge kidney Volume 7. Number

5 Indridason et al (9). It seems likely, therefore, that many patients with medublary sponge kidney have subclinical impairment of urinary acidification. Proton secretion may be impaired in cystic terminal collecting ducts. If only a fraction of the terminal collecting ducts are cystic, the patient may still be able to maintain normal systemic ph and excrete maximally acid urine (ph < 5.3) in response to ammonium chloride loading. Increased urine ph within cystic ducts, however, may promote intraductal precipitation of calcium apatite and bead to clinical stone disease. Although impaired urinary acidification may characterize many patients with medulbary sponge kidney, it does not follow that alkali therapy will be beneficial (see the Treatment section). Hypercalciuria In large series of cases of medullary sponge kidney, the prevalence ofhypercalciuria Is approximately 40% (7, 14). Parks and coworkers found that hypercalciuria was no more prevalent in stone formers with medullary sponge kidney than in stone formers without medullary sponge kidney (7). In addition, the same causes of hypercalciuria are present in patients with medullary sponge kidney as in patients without the disorder (6,8, 15, 16). Table 3 lists the possible causes of hypercalciuria in patients with medullary sponge kidney. Some investigators have reported a preponderance of absorptive hypercalciuria (8), whereas others have reported a preponderance of renal hypercalciuria ( 1 7). Although physiologic regulation of calcium excretion occurs primarily In the cortical distal nephron under the influence of parathyroid hormone and calcitriol, calcium reabsorption does occur along the inner medullary collecting duct of the rat. Some researchers have speculated that impaired calcium reabsorption in the cystic ducts may cause the hypercalciuria of medulbary sponge kidney. In contrast, Higashihara and coworkers ( 1 7) have reported that metabolic acidosis causes renal hypercalciuria. These Investigators studied 1 6 patients with medulbary sponge kidney. Seven patients exhibited renal hypercalciuria. These patients had higher urine ph values in response to acid loading and lower plasma bicar- bonate concentrations (22.5 meq/l) than healthy control subjects. Six of the seven patients had low plasma bicarbonate concentrations. Administration of 2 to 4 g of sodium bicarbonate daily reduced calcium excretion from 5.05 to 2.91 mg/kg per day and reduced the frequency of stone passage. Osther et at. (13) studied ten women with bilateral medullary sponge kidney. Four women had incomplete distal renal tubular acidosis. When compared with the six patients without renal tubular acidosis. and with ten healthy women, these four patients had lower plasma bicarbonate concentrations, increased urinary excretion rates of calcium, and decreased urinary excretion rates of citrate. The practical implications of these findings will be discussed in the Treatment section. The robe of hyperparathyroidism in the hypercalciuria of medulbary sponge kidney is debatable. Hyperparathyroidism has been demonstrated in a few patients ( 1,6). In large series, however, the prevalence of hyperparathyroidism In patients with medullary sponge kidney is not different from that of patients with idiopathic calcium stone disease (6,7). Other tubular abnormalities that have been described include a vasopressin-resistant concentrating defect ( 1,9) and a decreased ability to excrete an acute potassium load ( 1 8); neither defect has proved to be clinically significant. CLINICAL MANIFESTATIONS Patients are asymptomatic until kidney stones, hematuria, or infections develop, typically in adult life. Stones occur in 50 to 65% of these patients (19-2 1). When compared with calcium stone formers without medulbary sponge kidney, calcium stone formers with the disorder have higher rates of stone formation (7). Although intrapapillary concretions are composed of an admixture of calcium apatite and calcium oxalate or of calcium apatite alone, pure apatite stones are rarely passed. Stone analysis demonstrates either pure calcium oxahate or an admixture of calcium oxalate and calcium apatite ( 1 ). It thus seems likely that calcium oxalate deposition occurs in the collecting system before final stone passage. Microscopic or TABLE 3. Hypercalciuria of medullary sponge kidney Etiology (Reference Number) Laboratory Findings Mechanism Absorptive Hypercalciuria (8) Urinary calcium excretion less than mg/mg creatinine after fasting and greater than 0.26 mg/mg creatinine after calcium loading (15,16) Penal Hypercalciuria (1 7) Urinary calcium excretion greater than mg/mg creatinine after fasting (15,16) Hyperparathyroidism Hypercalcemia; elevated serum parathyroid hormone level Supranormal intestinal absorption of calcium Impaired calcium reabsorption by cystic ducts and/or metabolic acidosis (17) Hypercalcemia Journal of the American Society of Nephrology 1127

6 Medullary Sponge Kidney and Congenital Hemihyperirophy frank hematurla can occur in the presence or absence of stones ( 1,22). Urinary tract infections occur more frequently in calcium stone formers with medullary sponge kidney than in calcium stone formers without the disorder and occur more frequently in women than in men (7). Perltubular Inflammation has been demonstrated in the absence of infection and may result in sterile pyuria (2,3,9). Nephrocalcmnosis Is also a frequent manifestation of medulbary sponge kidney. Parks and colleagues (7) reported that nephrocalcinosis is present in 15% of calcium stone formers with medullary sponge kidney and In 3% of calcium stone formers without medullary sponge kidney. Medullary sponge kidney is associated with several developmental and hereditary disorders (Table 4). Anomalies of the urinary tract, bile duct ectasia (Caroli s disease), congenital pyboric stenosis, Beckwith- Wiedemann syndrome, Ehbers-Danbos syndrome, Marfan s syndrome, polycystic kidney disease, and congenital hemihypertrophy have been reported in association with medubbary sponge kidney ( 1,4). An association with primary hyperparathyroidism Is a matter of debate. Congenital hemlhypertrophy is characterized by asymmetry of the body as a result of hypertrophy of all somatic elements (muscles, bones, nerves, vessels) of one or more body parts. Visceromegaly may be present as well. Congenital hemihypertrophy can involve part or all of one side of the body (complex ipsilateral hemihypertrophy), body parts on both sides (complex contrabaterab hemlhypertrophy), a single limb (simple hemihypertrophy), or one side of the face (hemifaclal hypertrophy) (23). CongenItal hemlhypertrophy has been estimated to occur In 1 In 40,000 live births (24). It is frequently associated with other developmental abnormalities such as congenital heart disease, polyand syndactyly. mental retardation, Proteus syndrome, Silver-Russell syndrome, and Beckwith- Wiedemann syndrome. Congenital hemihypertrophy is also associated with childhood tumors, particularly adrenal adenomas and Wilms tumors (24). Nephrogenic rests and other developmental abnormalities of the kidney and urinary tract have been reported In association with congenital hemihypertrophy (23,25). Up to 10% of patients with congenital hemlhypertrophy have medullary sponge kidney (26,27), and up to 25% of patients with medulbary sponge kidney have congenital hemihypertrophy (14). TABLE 4. Developmental and inherited disorders associated with medullary sponge kidney Congenital Hemihypertrophy Beckwith-Wiedemann Syndrome Congenital Pyloric Stenosis Caroli s Disease Urinary Tract Malformations Ehlers-Danlos Syndrome Marfan s Syndrome Polycystic Kidney Disease DIAGNOSIS Definitive diagnosis is made by intravenous urography (IVU). (Although our patient did not undergo IVU, It was thought that the constellation of clinical findings strongly supported the diagnosis of medulbary sponge kidney. It was not thought that IVU would affect his management.) Renal concretions, often arranged in small clusters in the papillae. may be seen on the initial plain film. With administration of contrast medium, ectatic tubules are imaged as striations radiating from the calyces (brush ). Cysts are imaged as round opacifications in the papillae ( bouquets of flowers or bunches of grapes ). Brushes and bouquets appear before opacification of the calyces and may persist after the contrast medium is cleared from the renal pelves ( 1 ). Firm radiographic criteria for the diagnosis of medullary sponge kidney have not been established. In a recent study, a minimum of three linear or round collections within one renal papilla was required for the diagnosis of medullary sponge kidney (6). In previous studies, more stringent criteria (Involvement of three or more papllbae or of both kidneys) were used ( 1,7,8). Another diagnostic difficulty arises when only diffuse opacification of the papillae (papillary blushing) is present. Papillary blushing is detected by urography in 4% of stone formers and in 3% of non-stone formers (6). Whether this finding should be considered normal or indicative of a mild form of medubbary sponge kidney is unclear. A pathologic diagnosis of medublary sponge kidney has been established in kidneys that demonstrated only papillary blushing on urography ( 1 ). Papillary blushing should be considered diagnostic of medullary sponge kidney if it appears before opaclfication of the calyces, persists after contrast medium has been cleared from the pelves, and is associated with papillary concretions or nephrocalcmnosis. Computed tomography (CT), ultrasonography, and retrograde pyelography have little utility in the diagnosis of medullary sponge kidney. CT without injection of contrast medium appears to be more sensitive than IVU for detecting papillary concretions (28). These concretlons, however, are not specific for medullary sponge kidney. IVU remains far superior to CT (even with injection of contrast medium) in the diagnosis of medullary sponge kidney because of its fargreater ability to image tubular ectasia ( 1,28). Plain radiographs of the abdomen with or without tomography can be obtained to assist in following the progression of nephrocabcinosls. TREATMENT There is no specific treatment for medullary sponge kidney ( 1 ). Urinary tract infections are treated with antibiotics. Patients who develop calcium stones may have primary hyperparathyroidism or may have any or all of the risk factors for idiopathic calcium stone disease. Evaluation of patients with calcium stones, then, should include measurements of the 24-h un Volume 7. Number

7 Indridason et al nary excretion rates of calcium, oxalate, uric acid, and citrate. If the serum calcium level is elevated, then the serum parathyroid hormone level should be measured. Therapy should be directed at the underlying abnormality. Thiazide diuretics may be prescribed for hypercalciunla and albopuninol for hyperunicosunia. The use of alkali therapy in patients with calcium stone disease warrants further discussion. Although many patients with medublary sponge kidney have impaired urinary acidification, it does not follow that alkali therapy will be beneficial. Alkali therapy should certainly be prescribed for those with systemic acidemia (complete renal tubular acidosis). In those with partial renal tubular acidosis or more subtle impairment of urinary acidification, however, alkali therapy may raise urine ph and may promote mntraductab precipitation of calcium apatite. On the other hand, the study by Higashihara et at. demonstrates that, in patients with renal hypercalciunia and low plasma bicarbonate concentrations, alkali therapy decreases urinary calcium excretion and may decrease the frequency of stone passage ( 1 7). It is also rational to prescribe alkali therapy for those with hypocitratunia (12,14,17). Stones within the collecting system may be treated with extracorporeal shock-wave lithotnipsy (ESWL). The role of ESWL in the treatment of parenchymal stones needs to be elucidated. A study of eight patients failed to demonstrate fragmentation or evacuation of parenchymal concretions after ESWL (20). Another study did demonstrate a reduction in the stone burden of the renal medulla in 1 7 of 22 kidneys treated with ESWL (29). Seven patients in this study reported a long-term decrease in frequency of stone passage. SUMMARY Although our patient did not undergo intravenous urography, we believe that the constellation of clinical findings strongly supported the diagnosis of medullary sponge kidney. There was no other explanation for the nephrocalcinosis. He did not have renal tububar acidosis, hypervitaminosis D, hyperparathyroidism, sarcoldosis, or hypercalcemia, and his history did not suggest the milk-alkali syndrome. Our patient demonstrates the association of medullany sponge kidney and simple hemihypertrophy. in view of his mother s history, one or both may be hereditary. Hypercalciunia and nephrocalcinosis are frequent manifestations of medublary sponge kidney. A thiazide diuretic was prescribed to decrease the urinary cabcium excretion rate and prevent progression of nephrocalcinosis, but he has refused to take it. Because he does not have renal tubular acidosis or hypocitraturia, alkali therapy is not indicated. A plain radiograph of the abdomen will be obtained every 6 months to detect progression of nephrocalcmnosis. REFERENCES 1. Yendt ER: Medullary sponge kidney. In: Schrier RW, Gottschabk CW, Eds. Diseases of the Kidney. 5th ed. Boston: Little, Brown and Company: 1993: Jaeger P, Portmann L, Ginabskl J, Campiche M, Burckhardt P: Dietary factors and medullary sponge kidney as causes of the so-called idiopathic renal leak of calcium. Am J Nephrol 1987:7: Higashihara E, Nutahara K, Tago K, Ueno A, Niijima T: Unilateral and segmental medullary sponge kidney: Renab function and calcium excretion. J Urol 1984:132: Fick GM, Gabow PA: Hereditary and acquired cystic disease of the kidney. Kidney Int 1994:46: Mayalb GF: The incidence of medullary sponge kidney. Radiology 1970:21: Ginaiski J, Portmann L, Jaeger P: Does medullary sponge kidney cause nephrohithiasis? Am J Roentgenol 1990:155: Parks JH, Coe FL, Strauss AL: Calcium nephrohithiasis and medullary sponge kidney in women. N Engl J Med 1982:306: O Neill M, Breslau NA, Pak CYC: Metabolic evaluation of nephrohithiasis in patients with medullary sponge kidney. JAMA 1981:245: Higashihara E, Nutahara K, Tago K, Ueno A, Niijima T: Medullary sponge kidney and renal acidification defect. Kidney Int 1984:25: Osther PJ, Hansen AB, Roehl HF: Renal acidification defects In medullary sponge kidney. Br J Urol 1988:61: Backman U, Danielson BG, Felbstrom B, Johansson G, Ljunghall 5, Wikstrom B: Clinical and laboratory findings in patients with medullary sponge kidney. In: Smith LH, Robertson WG, Fmnlayson B, Eds. Urohithiasis: Chinical and Basic Research. New York: Plenum Press: 1981: Meyers AM, Whalley N, Martins M, Sonnekus M, Margolius LP: Recurrent renal calculi in patients with medullary sponge kidney. In: Ryall R, Bais R, Marshall VR, Rofe AM, Smith LH, Walker VR, Eds. Urohithiasis 2. New York: Plenum Press: 1994: Osther PJ, Mathiasen H, Hansen AR, Nissen HM: Unnary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney. Urol Int 1994:52: Harrison AR, Rose GA: Medullary sponge kidney. Unol Res 1979;7: Broadus AE, Dominguez M, Bartter FC: Pathophysiobogical studies in idiopathic hypercalciuria: use of an oral calcium tolerance test to characterize distinctive, hypercalciunic subgroups. J Clmn Endocninol Metab 1978:47: Pak CYC, Kaplan R, Bone H, Townsend J, Water 0: A simple test for the diagnosis ofabsorptlve, resorptive and renal hypercalciunla. N Engl J Med 1975:292: Higashlhara E, Nutahara K, Nlijima T: Renal hypercalciuria and metabolic acidosis associated with medullary sponge kidney: Effect of alkali therapy. Urol Res 1988: 16: Green J, Szylman P. Sznajder I, Winaver J, Better OS: Renal tubular handling of potassium in patients with medullary sponge kidney. Arch Intern Med 1984:144: Thompson IM, Rodriguez FR, Spence CR: Medullary sponge kidney and congenital hemihypertrophy. South Med J 1987:80: Vandeursen H, Baert L: Prophylactic role of extracorporeal shock wave hithotnipsy in the management of nephrocalcmnosis. Br J Urol 1993:71:392-39ff Nakada SY, Erturk E, Monaghan J, Cockett ATK: Role of extracorporeal shock-wave hithotripsy In treatment of urohithiasis in patients with medullary sponge kidney. Urology 1993:41: Journal of the American Society of Nephrology 1129

8 Medullary Sponge Kidney and Congenital Hemihypertrophy 22. Patriquin HB, O Regan 5: Medullary sponge kidney in childhood. Am J Roentgenol 1985:145: Stoll C, Alembik Y, Steib JP, de Saint-Martin A: Twelve cases with hemihypertrophy: Etiology and follow up. Genet Couns 1993:4: Bueno I, Ventura P, Samper MP, Perez Gonzalez JM, Bueno M: Congenital hemihypertrophy. Genet Couns 1993:4: Beckwith JB, Kiviat NB, Bonadio JF: Nephrogenic rests, nephrobhasomatosis, and the pathogenesis of Wilms tumor. Pediatr Pathol 1990:10: Tomooka Y, Onitsuka H, Goya T, et at.: Congenital hemihypertrophy with adrenal adenoma and medullary sponge kidney. Br J Radiol 1988:61: Sprayregen 5, Strasberg Z, Naidich TP: Medullary sponge kidney and congenital total hemihypertrophy. NY State J Med 1973:73: Ginaiski J, Schnyder P, Portmann L, Jaeger P: Medullary sponge kidney on axial computed tomography: Comparison with excretory urography. Eur J Radiol 199 1: 12: Holmes SAy, Eardley I, Cony DA, Nockler I, Withfield HN: The use of extracorporeal shock wave lithotripsy for medullary sponge kidneys. Br J Urol 1992:70: Volume 7. Number