Glomerular Lesions in Patients with Late-Onset Cystinosis with Massive Proteinuria

Abstract

3 siblings – 2 brothers aged 18 and 13 years, and 1 sister, aged 11 years – with adolescent or late-onset cystinosis presented with massive proteinuria. At the time their glomerular filtration rate was normal or only modestly diminished. Though glomerular injury was evident, renal tubular functional abnormalities were also present. Renal biopsy revealed histopathologic features typical of the nephropathic form of cystinosis with the Fanconi syndrome: polykaryocytosis, varying degrees of glomerular sclerosis, thickening and reduplication of basement membrane, fused foot processes, dilated tubules with altered epithelial cell features, and interstitial fibrosis. Fine granular deposits of C₃ and IgM are irregularly distributed in the glomeruli, findings which have not been described in cystinosis. These deposits are possibly immune complexes being deposited in the glomeruli unrelated to the cystine-storage disease or they may represent a localized activation of the complement system induced by the glomerular injury of cystinosis.

Late-Onset Nephropathic Cystinosis

“…Crystals were seen in three of the four biopsies carried out in our series. Our results are concordant with other reports in which cystine crystals were found in only one third of the patients who underwent renal biopsy (26,28,30); however, cystine crystals are water soluble and may be missed if certain precautions are not taken. The most striking lesion was FSGS, found in most biopsy specimens in published studies and in three of our four biopsies.…”

“…Renal biopsy data are available for approximately 15 patients from published studies (13,(25)(26)(27)(28)(29)(30)(31)(32)(33). Crystals were seen in three of the four biopsies carried out in our series.…”

Nephropathic cystinosis: late complications of a multisystemic disease

“…Fanconi syndrome also causes tubular proteinuria, with urinary losses of low molecular weight proteins such as retinol binding protein, albumin, and beta-2-microglobulin. Some pre-dialysis patients have had urinary protein levels in the nephrotic range [42,43].…”

Other Glomerular Disorders and Antiphospholipid Syndrome

“…Nephrotic syndrome may occur, and the glomerular lesions resemble FSGS except that crystals of cystine are found in glomerular and tubular epithelial cells. 3,31 Patients with cystinosis may also have blond hair, photophobia, hypothyroidism, corneal deposits, rickets, and Fanconi syndrome (see also Chapter 48).…”