Percutaneous renal biopsy may be necessary in a number of situations, such as establishing the exact diagnosis of a disease that may be secondarily involving the kidneys.¹ This is seldom the case in sarcoidosis, a systemic illness of unknown etiology characterized by noncaseating epithelioid-cell granulomatous tissue infiltration that canaffect virtually every organ. The diagnosis of sarcoidosis is generally established clinically, and/or by chest radiography abnormalities, with histologic confirmation, and with granulomas of other causes excluded.^2,3

Clinical renal involvement in sarcoidosis usually manifests as hypercalciuria, hypercalcemia, nephrocalcinosis, or nephrolithiasis (with or without obstructive uropathy and glomerular disease).² Only 7% to 27% of patients have histologic evidence of granulomatous interstitial infiltration resulting in impaired renal function.⁴ Almost all patients with renal dysfunction associated with granulomatous infiltration have concomitant systemic involvement of sarcoidosis, with clinical and laboratory data suggestive of the disease, which obviate the need for a renal biopsy.⁵

We report 3 cases of asymptomatic patients with unexplained renal failure in whom the cause of sarcoidosis could only have been found by use of a renal biopsy.

Patient 1

A 28-year-old black man presented with abrupt renal insufficiency for no apparent reason. His medical history was unremarkable, and he was taking no medications. Physical examination was remarkable only for a blood pressure of 140/100 mm Hg. Laboratory data were remarkable only for a serum creatinine of 2.7 mg/dL (normal range, 0.6-1.6 mg/dL); 1.5 years ago it was 1.1 mg/dL. Urinalysis was remarkable only for trace proteinuria. All other tests were normal.

Percutaneous renal biopsy revealed noncaseating, patchy granulomatous interstitial inflammation and giant cells, with acute and chronic inflammation, moderate tubular atrophy, and interstitial fibrosis consistent with sarcoidosis (Figure 1).

The patient was started on prednisone, 1 mg/kg once daily (60 mg/day), which was gradually tapered over 4 years and then discontinued. His serum creatinine declined and remained at 1.7 mg/dL.

Figure 1—Noncaseating granulomata (examples, red arrows) and patchy interstitial infiltrate (example, yellow arrow), with giant cells, inflammation, and moderate tubular atrophy and interstitial fibrosis.

Patient 2

An asymptomatic, previously healthy 53-year-old white woman presented with rapid deterioration of renal function. Physical examination and laboratory test results were normal, except for elevated serum creatinine, at 2.3 mg/dL (compared with 0.9 mg/dL 6 months ago). A renal biopsy specimen contained diffuse, acute interstitial noncaseating granulomatous inflammation, with significant destruction of the interstitium, as well as tubules with fibrosis and interstitial edema compatible with sarcoidosis (Figure 2).

She, too, was started on prednisone, 1 mg/kg once daily (60 mg/day), which was gradually tapered over 3 years and then discontinued. Her serum creatinine returned to baseline.

Figure 2—Diffuse, acute interstitial noncaseating granulomatous inflammation, with significant destruction of the interstitium, as well as tubules with fibrosis and interstitial edema.

Patient 3

A 75-year-old asymptomatic white woman presented with unexplained renal insufficiency. Her medical history was significant for long-standing but well-controlled hypertension with an angiotensin-converting-enzyme inhibitor. Physical examination and workup(similar to the previous 2 cases) were unremarkable. During the past year, her serum creatinine had risen from 1.1 mg/dL to 3.1 mg/dL.

Renal biopsy analysis showed that 27 of 29 glomeruli were sclerotic. Diffuse interstitial fibrosis and tubular atrophy with noncaseating granulomatous inflammation, including multinucleated giant cells, were all consistent with sarcoidosis.

In spite of the probability of advanced renal disease, once-daily prednisone of 1 mg/kg (50 mg/day) was started. It was gradually tapered over the next 1.5 years and then discontinued; her serum creatinine declined and remained at 2.5 mg/dL.

Discussion

Renal biopsy
Nephrologists use different criteria to decide when to perform a renal biopsy, which in large part is determined by the patient's signs and symptoms.^1,6 The information obtained by percutaneous renal biopsy often has great impact on the course of management and may alter therapy in up to 42% of cases.⁷

In acute renal failure, a renal biopsy is generally considered mandatory, provided that prerenal and obstructive causes have been eliminated, or when no spontaneous recovery of renal function is evident within 1 month of diagnosis.

In acute renal failure, only the timing of the biopsy, not the need for it, is controversial.⁶ Especially in cases of cryptic renal failure, physicians should proceed rapidly to biopsy to determine the cause of the renal failure. This ensures early treatment for a treatable disease, thereby potentially preventing further deterioration or reversing renal failure. Common treatable renal lesions are^6,8:

• Necrotizing vasculitis
• Crescentic glomerulonephritis
• Acute interstitial nephritis.

Sarcoidosis and renal failure
Sarcoidosis is seldom thought of as a cause for acute renal failure. It should always be included in the differential diagnosis of renal failure, however, because the renal lesion is often responsive to therapy.^5,9

Clinical diagnosis of sarcoidosis is generally straightforward because of its multi-organ involvement and the protean clinical manifestations. It rarely manifests with isolated renal failure, which would require a renal biopsy to establish its diagnosis.

When a biopsied renal specimen shows interstitial nephritis, the presence of granulomas is a helpful morphologic clue. Granulomas are encountered in sarcoidosis, allergic interstitial nephritis, rare cases of Wegener's granulomatosis, tuberculous or fungal pyelonephritis, dysproteinemias, and in the tubulointerstitial nephritis and uveitis syndrome.¹⁰

In the case of our 3 patients, the history, physical examination, lack of drug exposure known to cause interstitial nephritis, serologic testing, clinical course, and imaging studies ruled out other causes and established sarcoidosis with granulomatous interstitial nephritis as the cause of renal failure. At the time of presentation, all 3 patients lacked extrarenal clinical, laboratory, or radiologic manifestations of sarcoidosis, and the biopsy was the only means of establishing the diagnosis. The rapid institution of therapy based on the biopsy results allowed for the preservation of and improvement in the patients' renal function.

Review of the literature indicates that such an exclusively renal presentation of sarcoidosis is rare.¹¹ The overwhelming majority of patients with sarcoidosis and renal involvement have other signs or symptoms of systemic disease, with laboratory findings such as hypercalcemia or abnormal chest x-rays that facilitate making the diagnosis. Renal involvement in sarcoidosis more often presents as obstructive uropathy, nephrocalcinosis, or glomerular disease than as interstitial granulomatous infiltration.² In these 3 patients, sarcoidosis was not initially suspected and could only have been established by the renal biopsy.

Steroid therapy
Sarcoid granulomatous interstitial nephritis generally has a favorable response to corticosteroids, particularly if the inflammatory process involves an acute component. In a retrospective analysis of 39 patients with sarcoid interstitial nephritis, all those who were treated with corticosteroids showed an improvement in renal function.¹²

Nevertheless, renal function does not often return to normal after steroid therapy. This is likely the result of the frequently observed chronic, irreversible fibrotic changes seen on the biopsy. Preventing these fibrotic changes by early diagnosis and therapy is necessary to maximize the chance of response to treatment. Even with severe chronic histologic changes, however, an attempt at therapy is usually indicated, because the renal involvement may be "spotty," making a sampling error possible. This was demonstrated in patient 3, who had "far-advanced" renal disease as interpreted by the histologic changes; nevertheless, she responded to treatment. Such a response has been previously described.⁹

The corticosteroid dose generally recommended is 1 mg/kg daily; the duration of therapy varies widely, with up to 3 years or more of therapy needed.⁹ In addition, relapses can occur if steroid therapy is tapered too rapidly. In a review of 5 patients, the only 1 who relapsed had received less than 20 mg/day of prednisone for the first 3 months.¹¹

Our 3 patients demonstrated the variable response to therapy reported in the literature.^9,11 Significant improvement in renal function was observed in patient 1 only after 6 months of therapy, compared with 1 and 3 months, respectively, for patients 2 and 3.

Conclusion

Acute renal failure without an "apparent" cause or resolution is an indication for an immediate renal biopsy to prevent further renal deterioration and allow for immediate treatment. Although sarcoidosis usually presents with many clues, it may present solely as acute renal failure. This type of sarcoidosis is a steroid-responsive disease, and prompt diagnosis and therapy are, therefore, crucial for the prevention of irreversible renal damage. These 3 cases demonstrate the role of renal biopsy in establishing the cause of unexplained, acute deterioration of renal function. Without the information provided by biopsy, treatable disease may go undiagnosed.

References

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