The glomerulopathy of homozygous sickle hemoglobin (SS) disease: morphology and pathogenesis.

This morphologic and morphometric study of native-kidney biopsies of six homozygous sickle hemoglobin (SS) nephrotics defines a distinctive glomerulopathy of focal sclerosis developing in maximally hypertrophied glomeruli. In each biopsy, two patterns of segmental glomerulosclerosis were observed: a "collapsing" pattern and an "expansive" pattern. Morphologic analysis comparing group mean glomerular (Bowman's capsular) diameters indicates that glomeruli in SS are routinely markedly enlarged whether nephrotic (group SSN, 233.6 mu +/- SE of 25.3 [N = 6]) or not (control group SSC, 243.5 mu +/- SE of 12.5 [N = 5]). These values are significantly larger when compared with those of matched normal controls (group NC, 158.0 mu +/- SE of 12.7 [N = 6]) or to matched patients with idiopathic focal glomerulosclerosis (group IFS, 188.2 mu +/- SE of 17.9 [N = 6]). Furthermore, based on a previous study, it is most likely that glomerular enlargement in SS represents the maximal hypertrophy attainable in humans. Correlating observations of renal homografts in two sickle hemoglobin patients that developed segmental sclerosis of only the collapsing pattern soon after transplantation, it is proposed that in homozygous sickle hemoglobin nephrotics the collapsing pattern of segmental glomerulosclerosis represents an initial but progressive obliteration of the glomerular capillary bed by red blood cell sickling which cannot be compensated by further glomerular hypertrophy. Hemodynamic glomerular injury then supervenes from the sustained or increasing hyperfiltration in a diminishing capillary bed, manifesting morphologically as the expansive pattern of sclerosis.