Novo (new-onset) glomerulonephritis is that which occurs in a transplant recipient whose original kidney disease was either not glomerular or was of a different pathological type. Typically most appear a year or later after the kidney transplantation. De novo posttransplant glomerular diseases have the same pathological features as native diseases of the respective glomerular type when fully developed or sometimes modified by the ongoing immunosuppressive therapy. This may occur with or without other posttransplant pathologic findings that include a component of acute or chronic rejection or an infection. Obtaining information about the original renal disease is useful to determine de novo or recurrent status of the glomerular disease in the renal allograft. The most common de novo glomerular diseases are membranous glomerulopathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, pediatric donor-associated size mismatch glomerulopathy, anti-GBM disease in Alport syndrome cases, and drug-induced thrombotic microangiopathy.
A definitive diagnosis is made following a systematic examination of the renal biopsy for light, immunofluorescence, and electron microscopy.
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) (FIGURES 70-1 AND 70-2)
Focal segmental glomerulosclerosis. Glomerulus showing a segmental scar/sclerosis with capsular adhesion and intracapillary foam cells, covered by hyperplastic podocytes. The rest of the glomerulus appears normal with thin capillary walls and patent lumina. There is diffuse foot process effacement by electron microscopy. ×400, Trichrome stain.
Pediatric donor/size-mismatch glomerulopathy. Electron micrograph of glomerular capillary basement membranes showing focal irregular widening in the lamina rara externa (subepithelial) areas, with rarefaction and lamellations and intact lamina densa, and preserved foot processes, mostly related to hyperfiltration and stress injury. ×15,000, Uranyl nitrate and lead citrate.
INCIDENCE: 10–20% of renal allografts.
RISK FACTORS: Long-standing chronic vascular damage; size-mismatched (pediatric) kidney grafts; grafts with severe vascular disease; grafts with chronic transplant glomerulopathy; chronic calcineurin inhibitor–induced glomerulopathy; and viral infections such as hepatitis B and C virus, parvovirus B19, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Medications such as mammalian target of rapamycin (mTOR) inhibitors can also cause podocyte injury resulting in focal segmental glomerulosclerosis (FSGS). If all secondary causes are excluded, the diagnosis of idiopathic FSGS occurring in the kidney transplant can be made, which is extremely rare. Pediatric donor/size-mismatch glomerulopathy can also lead to similar pathology findings.
CLINICAL FEATURES: Eighty percent develop nephrotic-range proteinuria or they present with hypertension, hematuria, and acute allograft dysfunction.
Consider and treat secondary cause
All receive anti-proteinuric agents and antihypertensive medication.
If idiopathic, first line of treatment is high-dose steroids and cyclophosphamide (replace the antimetabolite from the transplant regimen), followed by intravenous gammaglobulin (IVIG) and plasmapheresis. Second line is cyclosporine, rituximab, and galactose.
ALLOGRAFT PROGNOSIS: The recipients with de novo FSGS and ...