Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study

Abstract

Background and objectives: The therapy and outcome of HIV infection have dramatically changed over the last 15 years, resulting in a change in renal complications. This study analyzed the characteristics of HIV-infected patients and biopsy-proven tubulointerstitial nephropathies to define disease patterns and therapeutic implications.

Design, setting, participants, & measurements: A clinico-pathologic retrospective study of 59 consecutive renal biopsies showing predominant tubular and/or interstitial lesions in HIV-infected patients referred to the nephrology department between 1995 and 2011 was performed. HIV-associated nephropathy and vascular diseases were excluded from the study.

Results: Tubulointerstitial nephropathies accounted for 26.6% of 222 native renal biopsies performed in HIV-infected patients. Two pathologic groups were analyzed, tubulopathy and interstitial nephritis, which represented 49% and 51% of tubulointerstitial nephropathies, respectively. Most patients presented with AKI (76.3%) and high-grade proteinuria (57.7%). Drug-related nephrotoxicity was the leading cause (52.5%). Alternative etiologies included infections (15.2%), dysimmune disorders (8.5%), malignancies (3.4%), and chronic (10.2%) and acute (10.2%) tubulointerstitial nephropathies of undetermined origin. Tubulopathy was strongly associated with antiretroviral drug toxicity (75.9%) and mostly caused by tenofovir (55.2%), which was associated with proximal tubular dysfunction (87.5%), overt Fanconi's syndrome (37.5%), and nephrogenic diabetes insipidus (12.5%). Interstitial nephritis was associated with a broader spectrum of pathologic lesions and etiologies.

Conclusions: In this series, tubulointerstitial nephropathies accounted for 26.6% of renal diseases in HIV-infected patients. Considering the therapeutic implications of diagnoses of drug toxicity, infection, and dysimmune syndromes, this study underscores the importance of monitoring renal parameters in HIV-infected patients and points to the relevance of kidney biopsy to allow an accurate diagnosis.

Figure 1.

Light microscopic and ultrastructural findings in patients with tubulopathy related to tenofovir nephrotoxicity. (A) Toxic acute tubular necrosis affecting the proximal tubules that associated loss of brush border, cytoplasmic reduction, luminal enlargement of tubular sections, epithelial desquamation, and interstitial edema and fibrosis (trichrome stain, ×400). (B) A higher-power view showing swelling and vacuolization of proximal tubular cell cytosol (trichrome stain, ×600). (C) Presence of red intracytoplasmic inclusions (arrows) in proximal tubular epithelial cells (trichrome stain, ×1000). (D) Ultrastructural examination showing abnormally enlarged and dysmorphic mitochondria within a proximal tubular epithelial cell. Original magnification, ×8000.

Figure 2.

Light microscopic findings in patients with interstitial nephritis. (A) Granulomatous interstitial nephritis associated with tuberculosis characterized by epithelioid granulomas with multinucleated giant cells (arrows) and necrosis (hematoxylin and eosin, ×200). (B) Foscarnet-related crystal nephropathy. The glomerular tuft is partially obliterated by clear foscarnet crystals (trichrome stain, ×400). Some crystals were also seen within tubular lumens, and the renal interstitium showed mild to moderate interstitial fibrosis and tubular atrophy. (C) Interstitial nephritis associated with diffuse infiltrative lymphocytosis syndrome characterized by dense cellular infiltrates composed of lymphocytes, monocytes, and plasma cells (hematoxylin and eosin, ×200). Immunophenotyping analysis shows that lymphocytes were mainly CD3+ and CD8+ T cells (Inset, ×200). (D) Interstitial nephritis related to immune reconstitution inflammatory syndrome (trichrome stain, ×200). The interstitial inflammatory infiltrate was mainly composed by CD68+ macrophages (Inset, ×400).