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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2006  |  Volume : 17  |  Issue : 2  |  Page : 216-221
Reversible Renal Failure in Hypertensive Idiopathic Nephrotics Treated with Captopril

Paediatric Nephrology and Hypertension Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria

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Angiotensin converting enzyme inhibitor (ACEI)- induced acute renal failure (ARF) is not as commonly reported in children as in adults. We report two cases of idiopathic nephrotic syndrome that developed ARF following captopril (an ACEI) treatment for prednisolone-induced hypertension. The two cases further alert us to the potential risk of ACEI-induced ARF in any nephrotic child on ACEI treatment. Low or high dose ACEIs should be given with extreme caution in active nephrotics in view of their relative hypovolemic state that may provoke ARF. The nephrotic children, who must be treated with ACEIs with or without diuretics, should be closely monitored for the development of ARF during the use of ACEIs.

Keywords: Cyclophosphamide, Hypertension, Oliguria, Proteinuria, Seizures.

How to cite this article:
Olowu WA, Adenowo OA, Elusiyan JB. Reversible Renal Failure in Hypertensive Idiopathic Nephrotics Treated with Captopril. Saudi J Kidney Dis Transpl 2006;17:216-21

How to cite this URL:
Olowu WA, Adenowo OA, Elusiyan JB. Reversible Renal Failure in Hypertensive Idiopathic Nephrotics Treated with Captopril. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2022 Aug 15];17:216-21. Available from: https://www.sjkdt.org/text.asp?2006/17/2/216/35794

   Introduction Top

The nephrotic syndrome (NS) is a major renal disorder in children.[1],[2],[3] It has generated tremendous research interests especially with regard to its pathogenetic mechanisms [4],[5],[6] and control of associated massive proteinuria.[7],[8],[9],[10],[11]

The angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have advanced in popularity as reno-protective drugs. [11],[12] In spite of their reno-protection, the ACEIs could be com­plicated by acute renal failure in adults [13],[14],[15],[16],[17],[18] and children. [19],[20],[21]

We report two cases of idiopathic nephrotic syndrome who developed ARF following treatment with captopril (an ACEI) for prednisolone-induced hypertension.

   Case Reports Top

Case 1

This is a 15-year-old girl who was admitted because of fever, cough, breathlessness and abdominal pain. Her past history was remarkable for recurrent generalized body swelling one year prior to admission and treatment with diuretics and oral prednisolone.

On admission, the patient was conscious, restless, and dyspnoeic. Her vital signs were temperature: 38.6 0 C, respiratory rate: 40/min and pulse rate: 120/min and blood pressure: 110/80 mmHg. She had facial puffiness, bilateral fine crepitations and rhonchi in the chest, massive ascites (abdominal girth, 107.5 cm) with a positive rebound abdominal tender­ness and absent bowel sounds. The vulva and both legs were severely edematous. The patient weighed 58 kg (>50th percentile for age and gender) and was 152 cm tall (<10th percentile).

The chest x-rays revealed minimal pleural effusion with bilateral patchy peri-hilar opacities, while the abdominal x-rays showed evidence of functional intestinal obstruction. The renal ultrasound revealed the dimensions in the left and right kidneys to be 11.5 x 5.8 x 1.1 cm and 11.1 x 4.7 x 0.8 cm, respectively. The urinalysis revealed 4+ proteinuria, 3-7 red blood cells/ high power field (hpf) but no ova or parasites. The 24-hour urine protein was 10.3 g/ 1.73 m 2 . The results of the blood investigations included creatinine 67.3 µmol/L, estimated glomerular filtration rate (GFR) (as determined from Schwartz formula): [22] 113 ml/min/1.73m 2 , albumin 14 g/L, cholesterol 9.23 mmol/L, electrolytes within normal limits, erythrocyte sedimentation rate 105 mm/hr, hematocrit 30%, white blood cell count 15,200/ µL (neutrophils 75%, lymphocytes 23%, eosinophils 2%), platelets count 283,000/µL and reticulocyte counts 1%. Other investi­gations included hemoglobin electrophoresis: AA, Coombs test: negative, lupus erythematosus cell: negative, VDRL: negative, human immuno­deficiency virus: negative, hepatitis B and C viruses' serology tests: negative and thin and thick blood films: neagative for malaria parasites (especially P.malariae). The pleural aspirate, blood and urine cultures were sterile but ascitic fluid culture grew Strept. pneumoniae.

The initial management of the patient included intravenous (IV) ampicillin and cloxacillin, and daily IV frusemide 1.0 mg/kg combined with 10 ml/kg of plasma infusion.

On day 14 of admission, oral hydro­chlorothiazide 2 mg/kg/day and spironolactone 2 mg/kg/day were replaced for the frusemide to avoid severe intravascular volume depletion. The protein intake was 2.5 g/kg/day and the daily salt intake was restricted to 0.5 mmol/kg. The infection responded very well to the antibiotic therapy and the patient's weight and abdominal girth decreased to 53 kg (<50th percentile) and 97 cm, respectively.

Oral prednisolone 60 mg/m 2 /day was added at the end of 3 rd week of admission. However, the patient developed severe hypertension (BP150/100 mmHg, >95th percentile for age and gender) [23] after two weeks of prednisolone therapy. This warranted introduction of captopril, 0.4 mg /kg/day in two divided doses and spironolactone was discontinued. At this stage, the patient's weight and abdominal girth increased to 61 kg (>75th percentile) and 105 cm, respectively. The serum creatinine and the estimated GFR were 77.3 µmol/L and 98.4 ml/min/1.73 m 2 , respectively, 24 h before the initiation of the captopril therapy.

After Five days on captopril therapy the patient became oliguric (urine volume < 250 mL/m 2 /day), drowsy, and started to vomit. Her blood pressure was 140/95 mmHg. The serum creatinine and the estimated GFR were 230 µmol/L and 33 ml/min/1.73m 2 , respectively.

The ARF was ascribed to captopril, which was switched to lacidipine (a calcium channel blocker); prednisolone, and hydrochlorothiazide were discontinued. The creatinine and estimated GFR returned to baseline with conservative management.[24] The oliguric and diuretic phases of the ARF lasted 9 and 13 days, respectively. Lacidipine was withdrawn on the 3 rd day of diuresis. The weight and abdominal girth at the end of diuretic phase were 46 kg (< 25th percentile) and 85 cm, respectively. The blood pressure was 100/60 mmHg. A kidney biopsy was performed on 60 th day of admission and was compatible with focal segmental glomerulosclerosis (FSGS). The patient was treated later with IV dexamethasone and cyclophosphamide and alternate day dose of prednisolone and complete remission was achieved within three weeks of therapy during her stay in the hospital without further complications.

The patient was discharged for home on the 91 st day and maintained a sustained remission nine months after discharge.

Case 2

This is a 12-year-old boy who presented with fever for one week with right lower back pain. His past history was remarkable for recurrent generalized body swelling and frothy urine for two years. He regularly received treatment in a peripheral hospital for his body swelling but could not specify the prescribed drugs.

The patient was febrile (Temp 38.2 0 C) and malnourished. Angular cheilitis was present bilaterally and facial edema was moderate. He was not dyspnoic; respiratory rate was 26 /min and blood pressure was 100/70 mmHg. The chest was clear, but ascites was moderate (abdominal girth, 76 cm) without abdominal tenderness. Pitting bipedal edema was moderate. Both gluteal muscles were atrophied. A warm, fluctuant, tender, oval-shaped swelling measuring 7 x 4 cm was palpable over the right lumbar region; a test aspirate yielded pus. He was 138 cm tall (< 10th percentile) and weighed 33 kg (<25th percentile).

The chest radiograph was unremarkable. Renal dimensions on ultrasound were 10.8 x 5.4 x 0.9 cm and 11.1 x 5.6 x 1.0 cm in the right and left kidneys, respectively. The urinalysis showed 4+ proteinuria, 2-5 pus cells/hpf, 3-8 red blood cells /hpf and granular casts. The urine and blood cultures were negative, while the lumbar abscess aspirate grew Staph. aureus. The ascitic fluid smear was negative for acid-fast bacilli and the tuberculosis skin test was non-reactive. The 24­hour urine protein was 4.6 g/1.73 m 2 . The results of the blood investigations included creatinine 50 µmol/L, estimated GFR: 138 ml/min/1.73m 2 , albumin 19 g/L, cholesterol 9.63 mmol/L, electrolytes within normal limits, erythrocyte sedimentation rate 115 mm/hr, hematocrit 26%, white blood cell count 12,800/µL (neutrophils 67%, lymphocytes 23%, eosinophils 2%) and platelets count 308,000/µL. Other investigations included hemoglobin electrophoresis: AA, Coombs test: negative, lupus erythematosus cell: negative, VDRL: negative, human immunodeficiency virus: negative, hepatitis B and C viruses' serology tests: negative and thin and thick blood films: negative for malaria parasites (especially P.malariae).

The initial management of the patient included a high calorie-protein diet in addition to multi­vitamin supplementation, IV cloxacillin and ampicillin for 2 weeks, incision and drainage of the lumbar abscess; the wound was dressed daily until it healed.

During the 4 th week of admission, the patient was started on oral prednisolone 60 mg/m 2 /day. The peripheral edema and ascites worsened after three weeks of prednisolone therapy; the weight and abdominal girth increased to 39 kg (<50th percentile) and 81 cm, respect­ively. The patient's blood pressure increased to 130/100 mmHg and captopril, 0.3 mg/kg/day and oral frusemide 1.0 mg/kg/day were started to control the hypertension. The prednisolone was continued, but the blood pressure increased to 140/120 mmHg by the end of the 4 th week of prednisolone treatment. The patient had severe headaches, with three episodes of tonic-clonic seizures during the same day. Each seizure episode was aborted with IV diazepam, 0.2 mg/kg/dose. The patient received IV hydralazine, 0.2 mg/kg/dose for rapid control of the hypertensive emergency. Two doses of hydralazine were given at 6 hour intervals. The prednisolone was there­after tapered to discontinue within a week.

The patient developed oliguric ARF eight days after starting the captopril, which was switched to lacidipine and the frusemide was discontinued. The patient became unconscious (Glasgow coma scale 9) on the 5th day of the onset of ARF. The blood pressure was 130/90 mmHg (diastole >95th percentile; MAP 103 mmHg). Financial handicap precluded dialysis for this patient; he was therefore managed conservatively. The oliguric phase lasted 11 days, while the diuretic phase lasted 9 days. The blood pressure gradually returned to normal with the onset of diuresis; lacidipine was stopped on the 2nd day of diuresis.

With five weeks of oral prednisolone and no remission, the patient was labeled as prednisolone resistant. A renal biopsy was performed on the 89 th day of admission. The result revealed membranoproliferative glome­rulonephritis (MPGN). The patient was started on immunosuppressive therapy com­prising IV dexamethasone and cyclophos­phamide on the 21 st day of the onset of diuresis. He went into complete remission with this regimen in addition to prednisolone 40 mg/m 2 alternate days for 12 weeks, then it was tapered to discontinue over four weeks. The patient re­mained in remission for 7 months after discharge.

   Discussion Top

FSGS and MPGN are one of the many morphological variants of steroid resistant NS that have been described in children. [25] Co-morbidities are not rare in childhood nephrotic syndrome. [25],[26] Peritonitis with ileus, pulmonary edema with pneumonia, malnutrition, lumbar abscess and hypertensive encephalopathy were observed co-morbidities in our cases.

In both cases, captopril-induced ARF during the treatment of prednisolone-induced hyper­tension resulted in the initial withdrawal of prednisolone and permanent discontinuation of captopril. Hypertension due to sodium and water retention is a known complication of steroid therapy. [27] The hypertension was worsened by avid sodium reabsorption by the renal tubules, which resulted from depleted intravascular volume due to the low plasma osmotic pressure secondary to the low plasma albumin level. Plasma albumin levels were severely low in both cases. In pediatric practice, the ACEls have become very popular in the treatment of hypertension, congestive cardiac failure and the nephrotic syndrome. [28],[29],[30],[31] We chose captopril for the treatment of hypertension in both patients, but the ARF aborted its continuation. These cases confirm earlier reports that administration of low-dose enalapril was associated with ARF in sick children.[19],[32] Furthermore, they were in agreement with earlier observations that ARF could occur days or months after ACEI therapy.[15],[19]

Some factors are known to promote the ACEls' induced ARF in susceptible individuals who have concurrent use of non-steroidal anti-inflammatory drugs, [14],[15] bilateral renal artery stenosis, [16] severe hypotension that can compromise the renal perfusion, [17] chronic renal insufficiency or volume depletion from diuretic therapy. When these factors exist in ACEI-treated patients, angiotensin II pro­duction and effect are reduced, and GFR may fall. [15] Of all these factors, the hypovolemic states and concomitant diuretic treatment possibly precipitated ACEI - induced ARF in our patients.

Delayed recovery from ACEI- induced ARF seen in our patients was similar to an earlier report in which oligoanuric phase of ACEIs induced ARF lasted 12 days before reso­lution. [19] Occasionally, recovery may not occur at all. [15]

We conclude that in view of the potential risk of ACEI-induced ARF, low or high- dose ACEIs should be prescribed with extreme caution in nephrotics with relative state of hypovolemia that may provoke ARF.

   References Top

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Correspondence Address:
Wasiu A Olowu
Paediatric Nephrology and Hypertension Unit, Obafemi Awolowo University, Teaching Hospitals Complex, PMB 5538, Ile-Ife
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Source of Support: None, Conflict of Interest: None

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