| Abstract|| |
Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure, where renal impairment tends to be variable but recovery is the rule. End-stage renal failure (ESRF) has been rarely reported as a complication of ATIN. We report here a case of idiopathic ATIN that resulted in severe acute renal failure. The patient developed ESRF, which required permanent renal replacement therapy.
Keywords: Acute, Interstitial, Nephritis, Chronic, Renal, Failure, Steroids.
|How to cite this article:|
Ghacha R, Rafi A, Abdelrahman M, Kumar SA, Karkar A. End-Stage Renal Failure as a Complication of Acute Tubulo-Interstitial Nephritis. Saudi J Kidney Dis Transpl 2005;16:321-5
|How to cite this URL:|
Ghacha R, Rafi A, Abdelrahman M, Kumar SA, Karkar A. End-Stage Renal Failure as a Complication of Acute Tubulo-Interstitial Nephritis. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2021 Apr 22];16:321-5. Available from: https://www.sjkdt.org/text.asp?2005/16/3/321/32861
| Introduction|| |
The term acute tubulo-interstitial nephritis (ATIN) is applied to a renal illness where inflammatory changes are mostly confined to the interstitium, but tubules are variably affected and glomeruli remain normal. ATIN may be idiopathic in origin, though it may result from hypersensitivity to different types of drugs. Though, the initial cases were described in association with extra renal infections,  ATIN may be secondary to a systemic illness or malignancies.
ATIN is an important cause of acute renal failure, where renal impairment tends to be variable but recovery is the rule. Although some patients may need dialysis or short courses of steroids for recovery, end-stage renal failure (ESRF) has been rarely reported as a complication of ATIN. , We report here a case of idiopathic ATIN that resulted in severe acute renal failure. The patient developed ESRF, which required permanent renal replacement therapy.
| Case Report|| |
A 38-year-old woman who had hypertension for one year treated irregularly with 50 mg atenolol once daily was hospitalized with complaint of nausea, vomiting and diffuse abdominal pain that started 20 days prior to admission. This was not associated with hematemesis, melena, loose motions, constipation or fever. The patient had no urinary or respiratory symptoms. She denied intake of any other drugs besides her antihypertensive. She had repair of anal fistula one year prior to admission and her renal functions were "normal at that time". She had no past history of diabetes mellitus. The patient was a mother of 2 children and her pregnancies had been normal. Both parents were diabetic and hypertensive.
Physical examination on admission showed BP 120/80 mmHg, Pulse 104/min, temperature 37°C and respiratory rate 20/min. No pallor, icterus or cyanosis. Jugular venous pressure (JVP) was not raised and no puffiness of face was detected. Nails were normal and there was no lower limb edema. The rest of the systems were unremarkable.
Laboratory results showed hemoglobin 106 gm/l, hematocrit 30%, WBC 11.05 x 10 3/µl and platelets 390 x l0 3/µl with 8% eosinophilia. Urinalysis showed albumin1+, negative glucose, WBC 0-3 and RBC 0-3 but no casts and urine culture showed no growth. The total 24-hour urinary protein was 900 mg and creatinine clearance was 2.6 ml/min. The blood chemistry results showed urea 84 mmol/l, creatinine 1320 µmol/l, potassium 6.7 mmol/l, chloride 98 mmol/l, calcium 2.3 mmol/l, phosphorus 1.9 mmol/l, magnesium 1.18 mmol/l, uric Acid 425 µmol/l, triglycerides 1.6 mmol/l, total protein 85 g/l, albumin 40 g/l, total bilirubin 1.7 mmol/l, GOT 15 u/l, GPT 14 u/l, GGT 36 u/l, alkaline phosphatase 113 u/l, LDH 25 u/l, CPK 28 u/l, glucose 5.56 mmol/l, amylase 240 u/l, PH 7.32, bicarbonate 11.9 mmol/l, PCO2 25 mmHg and PO2 100 rnmHg. Serologic investigations showed negative autoantibodies, normal C3 and C4, ASO titer normal. Anti-HCV, HBsAg and HIV were all negative.
The electrocardiogram was within normal limits and chest x- ray was normal. Echocardiogram study suggested pericarditis with minimal effusion.
Abdominal ultrasound showed bilateral enlarged kidneys with normal morphology and no hydronephrosis. Right kidney dimensions were 16 x 4.5 x 2.1 cm and left kidney 16 x 6.7 x 3 cm. Liver, spleen and gall bladder were all normal. Renal biopsy was examined by only light microscopy that showed generalized interstitial inflammation with edema. Lymphocytes, a few plasma cells and neutrophils were seen infiltrating the interstitium. A number of eosinophils were also seen. Tubulo epithelial damage was present focally. All the16 glomeruli in the biopsy were normal.
The history of this patient was extensively reviewed to look for a possible etiology, but no cause could be found, and the patient was considered to have acute renal failure due to idiopathic acute tubulo interstitial nephritis.
The patient was started on hemodialysis, though she maintained good urine output of 1.5-2 L /day. She developed catheter related gram negative septicemia and was prescribed appropriate antibiotics. The patient remained on hemodialysis for 4 weeks without any improvement in renal function. At this stage, she was commenced on intravenous methyl prednisolone 500 mg/day for 3 days followed by oral prednisolone 60 mg daily. One week later, the patient developed upper gastrointestinal bleeding from erosive duodenitis and histamine 2 (H2) blockers were started. Her bleeding stopped but she developed left lower limb deep venous thrombosis, probably as a result of the femoral vein catheterization where she was receiving anticoagulation treatment. However, despite the continuation of steroids for 4 weeks she showed no improvement in her renal functions.
After two months from her initial presentation, the patient was still in severe renal failure and required continuous hemodialysis. She refused a second renal biopsy and was discharged home on three times weekly hemodialysis prescription; the renal function did not recover ever since.
| Discussion|| |
This patient presented with acute renal failure of unknown etiology. Differential diagnosis in such cases includes acute tubular necrosis, acute tubulo interstitial nephritis and acute glomerulonephritis. Our patient's clinical and histological pictures were compatible with ATIN.
The term ATIN was initially described as a renal disease in patients with a number of infectious disorders where the kidneys were sterile.  These cases were described in association with scarlet fever and diphtheria.  The incidence of ATIN has declined after the introduction of antibiotics during the World War II, and the eradication of serious and fatal streptococcal infectious. However, the ischemic and nephrotoxic forms of ATIN have recently emerged as the predominant types of acute renal failure. In addition, interest in ATIN was revived in 1960 when it was found that antibiotics themselves could be the causative agents of tubular damage, whereas the dominant changes were confined to the interstitium. 
The exact incidence is unknown as the reported series is small and highly selective and patients with this diagnosis are often not biopsied. In two large renal biopsy series the incidence of ATIN was estimated as 1.21.3%. , However, Richet et al. in a study of 976 patients with acute renal failure noted that 14% of 218 biopsies were compatible with ATIN with an estimated incidence of 3%. 
Pathological changes in ATIN consist of interstitial edema, mononuclear cell infiltration and tubular injury with degeneration of varying severity. The interstitial changes are more marked in the cortex and outer medulla.
In most cases, symptoms develop weeks after exposure to the insulting agent. Symptoms include low grade fever, fleeting skin rash, mild arthralgia and flank pain. Hematuria is seen in 10-15% of the cases.
Urinalysis usually shows non-nephrotic proteinuria, pyuria and hematuria. Eosinophiluria is seen in 15% of the cases.  Sensitivity of eosinophiluria for the diagnosis of ATIN is estimated to be 40-60% and its specificity has not been well established; the positive predictive value is only 38%. 
Impairment of renal functions is variable and ranges from discrete abnormalities of tubular function to frank renal failure. Renal failure tends to be more marked in the older and oliguric patients. Duration of renal failure is also variable from few days to several weeks. Renal replacement therapy may be needed but reversal of renal failure is the rule. Persistent renal impairment can occur but is rare. , It is seen in patients showing marked interstitial fibrosis.  In two biopsies proven series with a total of 44 patients, 2 developed ESRF, 17 returned to normal renal function and the remainder recovered significantly but remained with varying degrees of renal impairment. 
There is some evidence that short courses of steroids improve renal lesions and hasten recovery in drug induced ATIN.  The use of steroids may be considered in patients with protracted renal failure. , Reversal of apparently permanent renal failure following steroid therapy of a patient on maintenance hemodialysis has been reported. 
Idiopathic ATIN is a well known entity that resembles the secondary form. Although laboratory evidence of hypersensitivity such as increased serum IgE, eosinophilia and eosinophiluria may be present, systemic manifestations are typically absent. ., Linear deposits of IgG, C3 and anti-tubular basement membrane antibodies have been detected. Furthermore, biopsy proven instances of ATIN with histological picture similar to drug induced ATIN, but without any drug exposure, have been reported.  Association of ATIN with uveitis, and bone marrow and lymph node granulomata have also been described.  This syndrome occurs predominantly in girls and young women. There are also granulomas in the kidney, but it must be distinguished from sarcoid nephropathy. Both ocular and renal changes respond ond to steroids but recurrence8 may occur.
Idiopathic ATIN may lead to irreversible renal failure, though recovery is the rule. Our patient developed ESRF, which is a very rare complication of ATIN. ESRF tends to develop in patients who are old, oliguric or show interstitial fibrosis on renal biopsy; our patient had none of these features. Furthermore, our patient failed to respond to steroids; one might speculate that steroids may be more effective in the secondary ATIN to drugs or infections than the idiopathic form. The role of cytotoxic drugs in such cases has not yet been explored. Our patient had a past history of hypertension (HTN) with a poor compliance to treatment but she did not have any signs of target organ damage and her renal biopsy did not reveal any hypertensive changes. Hence, it is unlikely that HTN may have precipitated the ESRF.
In conclusion, ATIN can at times present with severe and persistent renal failure requiring renal replacement therapy. This entity should therefore be considered in all patients presenting with severe renal failure of unknown etiology. ESRF is a rare outcome of idiopathic ATIN.
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Department of Nephrology, Kanoo Kidney Center, Dammam Central Hospital, P.O. Box 14563, Dammam 31434