Granulomatous interstitial nephritis: Our experience of 14 patients

Introduction

Although acute interstitial nephritis is a common cause of acute kidney injury, granulomatous interstitial nephritis (GIN) remains a rare condition. In the report of Mignon et al.,[1] granulomata were detected in only 0.95% of 3500 patients with renal biopsies. Drugs (37.5%) were the most common agent. Besides drugs, other etiologies commonly associated with GIN include, infections, immune processes, foreign body reaction, and some instances classified as idiopathic. There are not many published studies[123456] of GIN, and none from the Indian subcontinent. Tuberculosis being endemic in India, the causative agents of GIN is likely to be different from the other studies. The aim of the study was to analyze the etiology, clinical features and outcome of patients with biopsy-proven GIN at our institute from January 2000 to October 2012.

Materials and Methods

All renal biopsy records from January 2000 to October 2012 were scrutinized for the diagnosis of GIN. The clinical data were recorded from the case sheets of patients and also from outpatient (OP) records of the discharged patients. OP records were used to know the outcome of patients. The proforma included, the presenting history, past history, drug history, vital data, clinical examination, investigations, and management.

The renal biopsy slides were retrieved and reviewed. All slides were stained with H and E, periodic acid-Schiff, Masson Trichrome, Silver and Ziehl-Neelsen stains. In all patients, deeper sections were taken to expose the entire granuloma. Aggregates of epithelioid histiocytes with or without giant cells within the interstitium or perivascular region were labeled as a granuloma. In addition, the nature of granuloma was assessed for the presence of necrosis, confluence with or without giant cells and Schumann or asteroid bodies.

Patients with tuberculosis were treated with combinations of isoniazid (5 mg/kg/d), rifampin (10 mg/kg/d), pyrazinamide (10 mg/kg/d), ethambutol (5 mg/kg/d) and levofolaxacin (15 mg/kg/q 48 h, post hemodialysis). For the first 3 months four drugs were prescribed and for the next 6 months two drug were continued. No post-treatment prophylaxis was given.

Patients with other causes were treated after work-up for infection. Immunosuppresion was given accordingly with steriods, cyclophosphamide, and azathioprine. The offending factor was withdrawn.

Results

During the 13 year period 2798 renal biopsies were performed at our institute. There were 14 patients with GIN. GIN; therefore, accounted for 0.5% of patients. There were 8 (57.1%) males. The age was 35 ± 12 years, with a range of 20-70 years. All patients presented with renal failure and normal kidney size. The presenting serum creatinine was 6.7 ± 3.8 (range: 2.3-14.7) mg/dl. In nine patients tuberculosis was the causative agent. Drugs (phenytoin and carbamazepine) were the cause in two patients. Wegener's granulomatosis, systemic lupus erythematosis (SLE), and Immunoglobulin A nephropathy (IgAN), were the associated conditions in one patient each. Patient data have been described in Table 1.

Table 1 Details of patients with granulomatous interstitial nephritis

Discussion

We are herewith reporting 14 patients of GIN. This is the first case series from India. Prior to this there were a few case reports from India.[78910] There were five publications of case series of GIN. Recently, there was a review of GIN in allografts.[11] The age of patients was lower in our patients than these studies. While in our patients tuberculosis was a significant cause of GIN, in the previous studies dugs and sarcoidosis were leading causes and a higher percentage of (42.8%, 6 out of 14) required renal replacement therapy (RRT) in our patients [Table 2].

Table 2 Comparsion with the previous studies

The mean age was less than the other studies. This could be due to the dominance of tuberculosis. Tuberculosis is common in Indians in the age range of 15-54 years.[12] Mignon et al. and Javaud et al.,[13] reported tuberculosis as a cause of GIN in their series. This study highlights tuberculosis as a cause of GIN. Tuberculosis could also affect kidney by causing amyloidosis and focal proliferative glomerulonephritis.[14] We also reviewed glomerular lesions of tuberculosis.[15] Sarcoidosis and tubulointerstitial nephritis with uveitis (TINU) were not found to be a causative factor in our series. All patients were investigated fully for all possible causes of GIN, once granulomata were found in renal biopsy. Hence, missing the diagnosis of sarcoidosis and TINU was unlikely. Indeed, there were no previous articles published from India reporting GIN with sarcoidosis. Another feature of this article was only one patient had no etiological/diagnosis. The immunofluorescence of this patient suggested IgAN. Despite thorough investigation the cause could not be identified. IgAN presenting as GIN was reported before, but except for one report all had a cause for IgAN.[16] All patients in the present study had raised serum creatinine at presentation. This could explain greater requirement of RRT in our patients. GIN could be isolated or associated with the organ involvement orienting the diagnosis of underlying diagnosis. In the present study in seven patients tuberculosis was identified after GIN was diagnosed on renal biopsy.

In summary, GIN is a rare cause of renal failure with multiple etiology, which are treatable. In Indian subcontinent, tuberculosis is the most common etiology of GIN. Histologic features do not seem to identify the underlying cause of GIN. Clinical manifestations are also varied and do not distinguish the cause of GIN. Treatment of the underlying cause can reverse renal failure if it is not severe enough. In our study, many (42.8%) had stage five chronic kidney diseases.