What are immune mediated causes of chronic tubulointerstitial nephritis?
• Sarcoidosis
• Kidney involvement in sarcoidosis can occur in a variety of ways. Most commonly, patients have hypercalcemia secondary to increased production of 1, 25-dihydroxyvitamin D 3 by activated macrophages residing in granulomatous tissues. Hypercalcemia can lead to NDI, hypercalciuria-related nephrolithiasis, and, in some cases, kidney failure.
• Sarcoidosis can also present as a form of interstitial nephritis with associated noncaseating granulomas.
• Typical tubular manifestations include mild proteinuria, sterile pyuria, and impaired ability to concentrate urine.
• Treatment is with high-dose corticosteroids (prednisone up to 1 mg/kg per day).
• Sjögren syndrome: Sjögren syndrome–associated chronic interstitial nephritis characteristically presents as type 1 RTA with hypokalemia and a normal anion gap metabolic acidosis. Although the mechanism for this is incompletely understood, it is believed to be related to autoantibodies against carbonic anhydrase II. Treatment with immunosuppression may be helpful.
• Lupus nephritis: Isolated tubulointerstitial disease secondary to lupus is exceedingly rare. More commonly, tubulointerstitial disease is accompanied by glomerular involvement.
• IgG4 related disease: Kidney involvement is reported in up to one-third of patients with IgG4-related disease. The disease is characterized by a lymphoplasmacytic infiltrate, with increased numbers of IgG4-positive plasma cells, in the affected organ. A majority of patients also have elevated serum IgG or IgG4 levels. Patients with kidney involvement also may have hypocomplementemia. Most patients also have radiographic abnormalities consisting of small low-attenuation lesions. Raissian et al. have proposed diagnostic criteria for IgG4-related tubulointerstitial nephritis that includes histologic (>10 IgG4 staining plasma cells/hpf), imaging, serologic, and other organ involvement parameters.
• Tubulointerstitial nephritis and uveitis syndrome: Tubulointerstitial nephritis and uveitis (TINU) was first described by Dobrin et al. in 1975. It usually affects young females.
• The exact pathogenesis remains unclear, but the predominance of T lymphocytes in affected tissues and possible association with chlamydia and Epstein-Barr virus suggest that delayed-type hypersensitivity and cell-mediated immunity may play major roles.
• Clinically, patients present with nonspecific signs and symptoms (i.e., fever, generalized malaise, anemia, asthenia). Uveitis of the anterior chamber is seen bilaterally, presenting as redness and pain over the eyes. Uveitis may occur 2 months prior to, simultaneously, or up to 14 months after the onset of interstitial nephritis.
• Kidney manifestations include both proximal and distal tubular dysfunction. Increased urine β2 microglobulin (a marker of tubulointerstitial disease) has been noted. Ultrasonography may reveal enlarged, swollen kidneys.
• Definitive diagnosis is established by demonstrating typical findings of interstitial nephritis (i.e., tubulointerstitial edema with infiltration of lymphocytes, plasma cells, and histiocytes). Infiltration of CD4 and CD8 T lymphocytes, monocytes, and macrophages has been described. Eosinophils and noncaseating granulomas also may be seen.
• Other oculorenal syndromes include sarcoidosis and Sjögren’s (see above).
• Kidney disease frequently resolves spontaneously over the course of 12 months without steroid therapy. However, for those with moderately advanced CKD, prednisone 1 mg/kg per day may be given for 3 to 6 months. Although the kidney manifestations may resolve spontaneously and respond well to a course of systemic steroids, the uveitis often has a chronic or relapsing course that may require more aggressive therapy.
• Idiopathic hypocomplementemic interstitial nephritis: This disease entity is in older men with hypocomplementemia in the absence of lupus or Sjögren’s syndrome. Histopathology reveals extensive tubulointerstitial involvement and a predominantly lymphocytic infiltrate.
