Thrombocytosis‐related glomerulopathy in a patient with hyposplenia

A 3-month-old Japanese girl presented with failure to thrive. There was no family history of autoimmune or renal diseases. Anti-platelet antibody was not detectable in maternal serum. She was born at full term with no problems. Bodyweight was 3,010 g at birth. Physical examination was not significant other than the finding of low bodyweight (4,946 g: 1.59 SD). She gained weight well after the mother was given instructions on feeding. Laboratory data, however, were as follows: platelet count, 1,305 9 10/mm; urea, 11 mg/dL; creatinine, 0.48 mg/ dL; total protein, 6.8 g/dL; and albumin, 4.1 g/dL. The patient had hematuria and proteinuria; urinary protein to creatinine ratio (U-Pro/Cr) was 2.63. Ultrasonography indicated bilateral normal-sized kidneys with no anomaly. Abdominal computed tomography and Tc-Sn-colloid scintigraphy indicated nonfunctional polysplenia. Treatment with dipyridamole was started and U-Pro/Cr decreased to 0.83 (Fig. 1a). Renal biopsy was performed at 14 months of age. On microscopy, one out of 14 glomeruli had global sclerosis. Glomerular size was normal. Crescents and segmental sclerotic lesions were not observed. Other glomeruli showed diffuse mesangial proliferation (Fig. 1b). On immunofluorescence staining no deposits of immunoglobulins or complements were seen. Serum platelet-derived growth factor subunit B homodimer (PDGF-BB) was 2,328 pg/mL (normal: median, 220; range, 166–1,719). Marked expression of PDGF receptor (PDGFR)-b was observed in the mesangium of kidney specimens (Fig. 1c). In addition to dipyridamole, aspirin and saireito were added, but the degree of proteinuria remained unchanged (Fig. 1a). Candesartan was also commenced and U-Pro/Cr reduced to 0.28 (Fig. 1a). Interestingly, serum PDGF-BB also decreased to within the normal range (653 pg/mL), but dipyridamole, aspirin, and saireito had no effect on reducing serum PDGF-BB. At the time of writing the patient was 3 years old. Platelet count had decreased but still remained high (508 9 10/ lL) and creatinine remained unchanged (0.47 mg/dL). Glomerulopathy such as focal segmental glomerulosclerosis has been reported in patients with thrombocytosis. A close association has also been reported between the course of proteinuria and the disease activity of thrombocytosis. This indicates that there is a causal relationship between thrombocytosis and glomerular proteinuria, but the underlying mechanism of thrombocytosis-related glomerulopathy remains obscure. The expression of PDGF-BB and PDGFR-b is specifically increased and correlate with the progress of kidney glomerular lesions. Glomerulosclerosis and renal dysfunction were ameliorated by PDGF-BB/PDGFR-b in experimentally induced glomerulonephritis, suggesting that excessive PDGF-BB/ PDGFR-b signaling plays an important role in the progress of glomerular diseases. Previous reports showed that increased serum PDGF-BB and marked expression of PDGFR-b in the mesangium were related to essential thrombocythemia. In the present case, serum PDGF-BB was elevated and an increased expression of PDGFR-b was observed in the