An unusual renal complication in a patient with osteogenesis imperfecta

An Unusual Renal Complication in a Patient With Osteogenesis Imperfecta Lavjay Butani, MD, Julia A. Rosekrans, MD, Bruce Z. Morgenstern, and Dawn S. Milliner, MD

MD,

0 Osteogenesis imperfecta (01) is a common ‘rare’ disorder with a reported incidence of l/15,660 to l/20,666 in newborns. Skeletal abnormalities in this condition are so striking that its equally important and diverse extraskeletal manifestations frequently remain unnoticed. Sensorineural deafness, blue sclerae, myopia, easy bruisability, dental anomalies, and floppy mitral valves are some of its more frequently reported extraskeletal features. Other less common features include pulmonary hypoplasia, joint contractures, hydrocephalus, and osteogenic sarcoma.le3. Our patient, a 16-year-old boy, developed a previously unreported complication: chronic renal failure, which on subsequent evaluation was attributed to obstructive uropathy secondary to bony pelvic outlet deformities. 0 1995 by the National Kidney Foundation, Inc. INDEX

WORDS:

Osteogenesis

imperfecta;

pelvic

outlet

0

STEOGENESIS imperfecta (01) describes an uncommon group of variably inherited disorders, characterized by the presence of excessive bone fragility. The defect appears to be caused by an underlying qualitative or, less commonly, quantitative abnormality of the type I collagen molecule. Reported renal complications of osteogenesis imperfecta are nephrolithiasis and nephrocalcinosis. These have been attributed to possible renal outflow tract obstruction, with subsequent urinary stasis caused by the commonly encountered scoliosis.4 We report a patient with osteogenesis imperfecta who presented with an unusual and previously unreported complication: chronic renal failure, which on subsequent investigations was attributed to obstructive uropathy. CASE REPORT A 16.year-old boy presented to our institution with unexplained symptoms of anorexia, nausea, vomiting, and easy fatigability. His medical history was significant for a diagnosis of osteogenesis imperfecta with recurrent multiple fractures since birth, and a progressive thoracolumbar scoliosis. He denied any neurologic symptoms or voiding difficulty, but did report chronic constipation with nocturnal fecal incontinence, for which he was using mineral oil enemas on a regular basis. General physical examination was remarkable for a height of 115 ems (50th percentile for a 5.5year-old boy), weight of 33 kg (50th percentile for a IO.5year-old boy), lightly blue sclerae, and profound loss of muscle mass. His blood pressure at the initial visit was 170/120 mm Hg. The patient’s physical profile was compatible with type III osteogenesis imperfecta, with the presence of frontal bossing, triangular mid facies with widely spaced eyes (outer canthal distance, 10.5 cm, >97th percentile), bowing deformities of all extremities, pectus carinatum, and a

American

Journal

of Kidney

Diseases,

Vol 25, No 3 (March),

obstruction;

chronic

renal

failure;

protrusio

acetabuli.

severe thoracolumbar scoliosis. His hearing and dentition were both normal. Abdominal examination was remarkable for massive distension, presumably from fecal retention. Neurologic examination, including anal sphincter tone, was normal. Laboratory evaluation showed a hemoglobin of 6.3 g/ dL, serum creatinine of 3.2 mg/dL, blood urea of 134 mgl dL (normal range, 15 to 45 mg/dL), serum calcium of 9.1 mg/dL, serum phosphorus of 4.6 mg/dL, 24-hour creatinine clearance of 15 mL/min/1.73 m2 body surface area (BSA) and an iothalamate clearance of 12 mL/min/1.73 m2 BSA. The patient underwent anorectal manometry, which was normal. Computed tomography scan of the abdomen confirmed colonic dilatation with a normal-caliber rectum. The scan also demonstrated bladder enlargement with bilateral megaureters and pelvicalyceal dilatation. The colonic dilatation stopped abruptly at a point where several pelvic bone deformities were noted. It was believed that these changes indicated the presence of an extrinsic compressing cause. Plain radiography of the kidneys, ureters, and bladder showed multiple pelvic deformities with protrusio acetabulae. Extensive fecal material was seen in the rectosigmoid region, Intravenous pyelogram demonstrated bilateral pelvicalyceal dilatation with thin rim of residual renal parenchyma. The voiding cystourethrogram showed no evidence of vesicouretral reflux. An enlarged trabeculated urinary bladder with multiple small diverticuli was demonstrated. Some contrast material remained in the bladder at the end of voiding. Urodynamic studies indicated the presence of a hypotonic bladder

From the Division of Pediatric Nephrology, Department of Pediatrics and Adolescerzt Medicine, Mayo Clinic, Rochester, MN. Received June 8, 1994; accepted in revised form October 18, 1994. Address reprint requests to Dawn S. Milliner, MD, Division of Pediatric Nephrology, East 9 A, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905. 0 1995 by the National Kidney Foundation, Inc. 0272-6386/95/2503-0020$3.00/O

1995:

pp 489-491

489

BUTANI function, his most recent mm/l .73 m2 BSA.

iothalamate

clearance

being

ET AL 96 mL/

DISCUSSION

Fig 1. KUB demonstrating marked lumbar scoliosis with profound pelvic outlet contraction (arrows) due to the ‘trefoil’-shaped pelvis (protrusio acetabuli). Also note generalized osteopenia and pin fixations of femur fractures on both sides.

with a functional bladder capacity of 5 17 mL and a postvoid residual of 300 mL (Fig 1). Bilateral nephrostomy tubes were placed to determine if decompression of the dilated urinary tracts would result in improvement of renal function. Within 6 weeks of placement of the nephrostomy tubes, the patient’s serum creatinine decreased to 1.6 mg/dL, with an increase in his creatinine clear ante to 35 mL/min/m2 BSA. At this point, the nephrostomy tubes were removed, and the patient was managed on four times a day intermittent self-catheterization. He was followed regularly for the next 4 years. Although he continued to have recurrent fractures, his renal function remained stable with an iothalamate clearance of 27 mL/min/ m2 BSA. He was lost to follow-up for the next year, and when he reappeared at the clinic, he had developed recurrence of his original symptoms of anorexia, nausea, vomiting, and easy fatigability, along with new onset tetanic spasms. Repeat laboratory evaluation at that time showed a hemoglobin of 7.6 g/dL, serum creatinine of 11 mg/dL, blood urea of 258 mg/dL, serum calcium of 6.5 mg/dL, serum phosporus of 10.1 mg/dL, and a serum alkaline phosphatase of 673 units (bone fraction, 672). Hemodialysis was instituted, and in July 1993, a living related renal transplant was successfully performed. Posttransplant, the patient has continued intermittent catheterization four times a day and has had excellent and stable allograft

The widely used Sillence classification categorizes 01 into types I to IV on the basis of severeity of skeletal manifestations and presence of associated extraskeletal features. Type I and type IV 01 constitute the mild variants, with onset of skeletal abnormalities in the first year of life, and type II 01 is the perinatally lethal variant characterized by in utero skeletal deformities and a restrictive thoracic cavity leading to acute respiratory failure in the newborn period. Type III 01, which our patient had, is of intermediate severity and is associated with in utero fractures, marked skeletal osteopenia, and late cystic changes in the extremities. Pelvic deformities in osteogenesis imperfecta including protrusio acetabulae are relatively common findings because of frequent fractures and subsequent faulty remodeling of bones. A case report by Wenger et al5 described a patient with 01 with protrusio acetabulae resulting in colonic obstruction, although without any associated renal dysfunction. This patient was subsequently operated on for correction of his bony deformity, and hence may not have had sufficient time for progression of his protrusio to cause obstructive uropathy. With improved survival into adulthood attributable to early recognition of this disorder, improvement in supportive therapy, and availability of innovative surgical technology, we believe that many more patients with extraskeletal manifestations associated with 01 will be encountered. These problems should specifically be looked for in patients with severe skeletal deformities. There are several reports in the literature of patients with hypoplastic pelvic outlet associated with urinary tract anomalies, including renal agenesis.6 No reports are found in the literature of the association of 01 with neurogenic bladder. It may be argued that our patient was unfortunate in having two unrelated and rare anomalies, namely 01 and idiopathic neurogenic bladder. The clinical findings seem to indicate otherwise, although they are impossible to prove beyond doubt.

OSTEOGENESIS

IMPERFECTA

WITH

RENAL

FAILURE

REFERENCES 1. Rutkowski R, Resnick P, McMaster JH: Osteosarcoma arising in Osteogenesis imperfecta: A case report. J Bone Joint Surg 61:606-608, 1979 2. Lasson U, Harms D, Wiedmann HR: Osteogenic sarcoma complicating osteogenesis imperfecta tarda. Em J Pediatr 129:215-218, 1978 3. Reid BS, Hubbard JD: Osteosarcoma arising in osteogenesis imperfecta. Pediatr Radio1 8: 1 IO- 112, 1979 4. Vetter U, Maierhofer B, Mtiller M, Lang D, Teller WM,

491 Brenner R, Frohneberg D, Worsdorfer 0: Osteogenesis Imperfecta in childhood: Cardiac and renal manifestations. Eur J Pediatr 149: 184- 187, 1989 5. Wenger DR, Abrams RA, Yaru N, Leach J: Obstruction of the colon due to protrusio acetabuli in osteogenesis imperfecta: Treatment by pelvic osteotomy. J Bone Joint Surg 70:1103-l 107, 1988 6. Currarino G: Association of congenitally small pelvic outlet with hypoplasia of bladder and urethra, and absent kidneys. Am J Roentgen01 109:399-402, 1970