Nephrocalcinosis induced by furosemide in an adult patient with incomplete renal tubular acidosis

(Section Editor: G. H. Neild)

Adelaide Simões, Fernando Domingos and M. Martins Prata

Serviço de Nefrologia, Hospital de Santa Maria, Lisboa

Keywords: furosemide; hypercalciuria; hypocitraturia; nephrocalcinosis; renal ultrasonography

Although frequently described in children, medullary nephrocalcinosis associated with furosemide has rarely been described in adults.

Case

A 40-year-old female patient was referred to the outpatient renal stone clinic of the Santa Maria Hospital for investigation of nephrocalcinosis. She had a previous history of one single episode of renal colic 15 years earlier and had been self-administering furosemide (40–160 mg/day) ever since, allegedly due to persistent oedema. A few months previously, a blood test revealed a slight increase in creatinine and urea concentrations, and renal ultrasound performed at this time showed medullary nephrocalcinosis.

On examination the patient was 156 cm tall, weighed 47 kg and had normal blood pressure (110/70 mmHg). No oedema was observed and physical examination was normal. A renal ultrasound showed medullary nephrocalcinosis with total involvement of medullary pyramids (Figure 1Go). An abdominal plain film and renal computerized axial tomography (CAT) (Figure 3Go) confirmed this sonographic finding.



View larger version (117K):
[in this window]
[in a new window]
 
Fig. 1. Medullary nephrocalcinosis observed in the first renal ultrasound.

 


View larger version (139K):
[in this window]
[in a new window]
 
Fig. 3. The ultrasound image obtained 6 months after furosemide interruption to reveal a decrease in medullary hyperechogenicity.

 
Initial metabolic evaluation was performed with the patient still taking furosemide. According to our protocol, blood and 24-h urine samples were collected over 3 consecutive days. Concentrations of creatinine, calcium, phosphorus, uric acid, sodium, potassium and chloride were measured both in blood and urine; 24-h urine samples were also analysed for volume, pH, magnesium, oxalate and citrate. Intact PTH (iPTH) was measured in the blood. Renal function was normal (creatinine clearance 92 ml/min), there was hypokalaemia (minimum 3.1 mEq/l), normocalcaemia (9.5 mg/dl) and iPTH was elevated (maximum 248 pg/ml; normal range 12–72 pg/ml); urine analysis revealed a median volume of 3.4 l/24 h, pH 6.0, discrete hypercalciuria (maximum 259 mg/24 h) and marked hypocitraturia (minimum 0.3 mmol/24 h). All the other parameters analysed were normal. A parathyroid ultrasound was normal and a dual X-ray absorptiometry of the lumbar spine revealed osteopenia (bone mass density=0.918 g/cm2; T score=-1.5; Z score=-1.2).

Furosemide treatment was stopped and 1 week later, a further metabolic evaluation showed a rise of serum potassium to 3.6 mEq/l, normalization of iPTH (38.2 pg/ml), decrease of calciuria to 84 mg/24 h, increase of citraturia to 1.5 mmol/24 h and decrease of urine volume to 1400 ml/24 h. Because urine pH was sustained at 6.0, a tubular acidification test with NH4Cl was performed. Before the administration of NH4Cl, venous pH (VpH) was 7.40, venous HCO3- (VHCO3) was 26.2 mmol/l and urine pH (UpH) was 6.36. After oral charge with NH4Cl at a dosage of 0.05 g/kg/day for 3 days, VpH decreased to 7.30 and VHCO3 to 21 mmol/l. UpH was unable to fall below 5.98. These results were compatible with the diagnosis of incomplete renal tubular acidosis type I.

The patient was advised to remain off furosemide. Six months later there was a slight improvement of ultrasound images, with a decrease in medullary hyperechogenicity (Figure 3Go).



View larger version (133K):
[in this window]
[in a new window]
 
Fig. 2. Renal CAT scan, confirming the presence of medullary calcifications.

 

Discussion

The term ‘nephrocalcinosis’ means an increase in the calcium content of the kidney and is a relatively rare disease. It can take two different forms: medullary nephrocalcinosis is the most frequent form and is characterized by the exclusive involvement of the medullary pyramids. It is usually associated with renal tubular acidosis type I, as either its cause or consequence. Cortical nephrocalcinosis is rarer, involves all the renal parenchyma and is frequently associated with severe metabolic defects, such as primary hyperoxaluria or end-stage renal failure.

The association between nephrocalcinosis and long-term therapy with furosemide is well documented in infants [13]. Pyramidal involvement is present in ~64% of premature infants with low birth weight, treated with furosemide for long periods [1]. In adults, nephrocalcinosis induced by furosemide is rare and presents as medullary nephrocalcinosis without significant alteration of renal function (benign form).

Renal ultrasound is the most sensitive method for the diagnosis of nephrocalcinosis, and the sonographic finding of echogenic pyramids with a normally echogenic cortex is believed to be specific for medullary nephrocalcinosis [1,2]. Calcification may not be visible on the abdominal plain film, but CAT usually confirms the diagnosis.

In the present case, hypokalaemia, elevation of iPTH and osteopenia were attributed to long-term treatment with furosemide. The presence of renal tubular acidosis can be secondary to the tubular lesion, but a primary form cannot be excluded in this patient.

Furosemide should be part of the differential diagnosis list of medullary nephrocalcinosis in adults undergoing long-term therapy with this drug, especially if renal tubular acidosis is present.

Notes

Correspondence and offprint requests to: Dr Maria Adelaide de Lima Serra Simões, Serviço de Nefrologia, Hospital de Santa Maria, Av. Prof. Egas Moniz, 1699 Lisboa Codex, Portugal Back

References

  1. Solivetti FM, Paganelli C, Nasrollah N, Bacaro D, Quintigliano D, Zoffoli M. Nefrocalcinosi da trattamento prolungato com furosemide. Radiol Med1998, 95: 129–131
  2. Reuter K, Kleinman PK, DeWitt T, Fabian T. Unsuspected medullary nephrocalcinosis from furosemide administration: sonographic evaluation. J Clin Ultrasound1985, 13: 357–359[ISI][Medline]
  3. Alon US, Kaplan RA, Gratny LL, Nichols MA. Histological long-term outcome of furosemide-induced nephrocalcinosis in the young rat. Pediatr Nephrol1996, 10: 191–194[ISI][Medline]