Kidney nontumor / medical renal

• Kidney disease in sarcoidosis can manifest as
  • Granulomatous interstitial nephritis
  • Nongranulomatous interstitial nephritis
  • Nephrocalcinosis of the calcium phosphate and oxalate type
  • Nephrolithiasis
  • Sarcoidosis associated glomerular diseases

• Incompletely understood (see Lung - Sarcoidosis) (Respir Med 2020;173:106161)

• Granulomas are well formed concentrically arranged layers of immune cells with a central core of macrophages, epithelioid cells and multinucleated giant cells and an outer layer of loosely organized lymphocytes (mostly T cells) and interposed dendritic cells, sometimes surrounded by collections of B lymphocytes
• Epithelioid cells (epithelioid histiocytes) are derivatives of activated macrophages resembling epithelial cells (Wikipedia: Epithelioid Cell [Accessed 25 July 2024])
• Caseous necrosis is the grossly visible, cheese-like appearance of the granulomas; this term has no microscopy counterpart and thus, the term necrotizing is preferable (Arch Pathol Lab Med 2022;146:233)
• Sarcoidosis granulomas are most often nonnecrotic (Am J Respir Crit Care Med 2020;201:e26)
• Epithelioid cells are elongated, with pale eosinophilic cytoplasm and central, ovoid nuclei, which are less dense than that of a lymphocyte (Wikipedia: Epithelioid Cell [Accessed 25 July 2024])
• Presence of numerous noncaseating (nonnecrotizing) granulomas favors sarcoidosis (Am J Respir Crit Care Med 2020;201:e26)
• Sarcoid granulomas feature compact, tightly formed collections of large epithelioid histiocytes and multinucleated giant cells (Am J Respir Crit Care Med 2020;201:e26)
• These granulomas are confined to the renal cortex and stay discrete; interstitial inflammatory infiltration is observed in all cases (Am J Respir Crit Care Med 2020;201:e26)
• Blau syndrome
• Nongranulomatous interstitial nephritis may show numerous eosinophils in the interstitial infiltrate (Am J Respir Crit Care Med 2020;201:e26)
• Nephrocalcinosis manifests as calcium phosphate or oxalate tubulointerstitial deposits
  • Such deposits are also found in patients with granulomatous and nongranulomatous interstitial nephritis (Nephrol PoC 2019;5)
• Most frequent glomerular disease occurring in sarcoidosis is membranous glomerulopathy (Orphanet J Rare Dis 2013;8:65)
• Other glomerular diseases observed in patients with sarcoidosis include IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease and lupus nephritis (Orphanet J Rare Dis 2013;8:65)
• Focal segmental glomerulosclerosis and hypertensive nephrosclerosis may be found in sarcoidosis patients with interstitial nephritis (Sarcoidosis Vasc Diffuse Lung Dis 2018;35:252)

Contributed by Alexei Mikhailov, M.D, Ph.D.

A 46 year old woman, who has a history of pulmonary sarcoidosis diagnosed at the age of 25 years and is a frequent user of aspirin, underwent a CT with contrast due to a suspicion for a relapse of the disease. A week later, she developed a Clostridium difficile associated colitis, for which she received vancomycin treatment. She presents with acute kidney injury with serum creatinine of 3 mg/dL (baseline 1 mg/dL) and her urine contains eosinophils. A kidney biopsy is performed. It shows extensive focally accentuated tubulointerstitial inflammation involving the cortex and the corticomedullary junction; a representative image is shown above. You will report that, based on the clinicopathological data, the most likely etiology of the acute tubulointerstitial nephritis is

1. Aspirin
2. Computed tomography (CT) contrast material
3. Sarcoidosis
4. Vancomycin

D. Vancomycin. The image shows acute tubulointerstitial nephritis and in the center of the image, a loose collection of multinucleated giant cells and epithelioid cells is seen, indicating a poorly formed granuloma. Antibiotics, especially vancomycin, are a frequent cause of granulomatous interstitial nephritis characterized by poorly formed granulomas and corticomedullary junction involvement. Urine eosinophils are suggestive but not necessary for the diagnosis of drug related allergic interstitial nephritis. Answer A is incorrect because as opposed to other nonsteroidal anti-inflammatory drugs (NSAIDS) (indomethacin, ketorolac), aspirin has not been reported to cause granulomatous interstitial nephritis. Aspirin associated renal lesions are acute tubular injury, acute interstitial nephritis and minimal change disease. Answer B is incorrect because CT contrast media has not been reported to induce granulomatous interstitial nephritis. Acute tubular injury, isometric tubular epithelial vacuolization and acute interstitial nephritis are associated with iodinated contrast. Answer C is incorrect because well formed granulomas located in the renal cortex are characteristic for sarcoidosis .

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Reference: Sarcoidosis

A 55 year old man with multiorgan sarcoidosis affecting the lower respiratory tract, the skin and the eyes and a history of longstanding hypertension presents with mild elevation of serum creatinine. Kidney sarcoidosis is suspected and a kidney biopsy is done. The biopsy shows moderate arteriosclerosis and mild to moderate interstitial fibrosis and tubular atrophy with associated mononuclear infiltration. One of the biopsy cores shows an interesting structure. You examine this structure and your conclusion is

1. Artifact of tissue processing and staining; of no diagnostic consequence
2. Extratubal Tamm-Horsfall protein
3. Granulomatous interstitial nephritis, consistent with sarcoidosis kidney involvement
4. Necrotizing granuloma; need to order acid fast and GMS stains

B. Extratubal Tamm-Horsfall protein. The image shows 2 pools of glassy PAS+ material, characteristic for extratubal Tamm-Horsfall protein (uromodulin), surrounded by a mononuclear cell infiltrate. Tubular release of the uromodulin may occur in chronic renal diseases affecting the interstitium, such as in this case, with renal vascular disease associated tubular injury, atrophy and damage by immune cells. Interstitial uromodulin is typically surrounded by inflammatory cells and the mechanism of uromodulin release and its role in inflammation are currently not known (Am J Kidney Dis 2012;59:452). Answer A is incorrect because the observed pattern is characteristic for interstitial Tamm-Horsfall protein (uromodulin) with a surrounding reaction. Answer C is incorrect because there is no granuloma. Answer D is incorrect because there is no granuloma; the PAS+ material is interstitial Tamm-Horsfall protein (uromodulin).

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Reference: Sarcoidosis