Sept. 14, 2019
Mayo Clinic uses a comprehensive protocol for the prevention of glomerulonephritis (GN) after kidney transplant. Applied enterprise wide, the approach emphasizes early diagnosis utilizing surveillance biopsies and urine testing, early initiation of treatment even when the recurrent disease is clinically mild, and preventive treatment before transplant in certain patients.
"Our approach to prevention and treatment of recurrent disease is very proactive, starting in the pretransplant period and extending through post-transplant," says Mireille El Ters, M.D., a transplant nephrologist at Mayo Clinic in Rochester, Minnesota.
GN is the primary cause of end-stage kidney disease in as many as 30% of allograft recipients in the United States. "Recurrence of kidney disease poses a significant disease burden," says Martin L. Mai, M.D., a transplant nephrologist and medical director of the Kidney Transplant Program at Mayo Clinic in Jacksonville, Florida. "After transplant, patients feel they have a new life. There's a huge bump in the road when a biopsy shows the disease has come back."
Recurrent GN can remain clinically silent for months to years. Relying on clinical and laboratory parameters alone will likely miss early recurrence. In addition, certain forms of recurrent GN are generally aggressive. "If they're not recognized and treated quickly, these recurrent diseases can lead to early loss of the allograft," Dr. El Ters says.
As a major center for kidney disease and transplantation, Mayo Clinic has extensive expertise in preventing GN after kidney transplant. "Our transplant nephrology teams from all three campuses meet regularly. We are a close-knit group with a substantial knowledge base that is actively shared across the three sites," says Hasan A. Khamash, M.D., a transplant nephrologist and medical director of the Kidney Transplant Program at Mayo Clinic's campus in Phoenix, Arizona.
Close surveillance and preventive measures
Before kidney transplantation, Mayo Clinic transplant nephrologists carefully review the patient's history and existing laboratory testing. Renal slides from outside institutions may be brought to Mayo and reinterpreted by Mayo's renal pathologists. Additional testing that can help predict the risk of disease recurrence — such as autoimmune, functional complement and genetic testing — may be performed.
After transplantation, patients remain in town and are observed closely for three weeks. After that, patients return to the clinic at four months and 12 months post-transplant, then annually.
Between visits, patients are monitored with a standard outpatient laboratory tests panel. In patients with high risk of GN recurrence, that panel includes measurements of microalbuminuria. "Any sudden change can be a red flag," Dr. Mai says. If test results between clinic visits are concerning, patients are quickly seen again at Mayo Clinic.
Protocol biopsies are done at four, 12, 24, 48, 84 and 120 months after kidney transplantation. In addition to standard light microscopy, immunofluorescence testing and electron microscopy (EM) are used to evaluate the biopsies.
"EM is very sensitive at detecting early disease in multiple kidney conditions — most importantly, the early recurrence of focal segmental glomerulosclerosis (FSGS), which presents initially with normal light microscopy and first shows changes on EM," Dr. El Ters says. "Certain recurrent monoclonal protein-related diseases are also detected at earlier stages with immunofluorescence testing and EM."
In a study published in the July 2019 issue of Transplantation, Mayo Clinic researchers demonstrated the potential benefits of tissue biopsies for patients with recurrent proliferative GN with monoclonal immunoglobulin deposits (PGNMID). Twenty patients with the disease were monitored post-transplant for recurrence. Eighteen of the 20 grafts (90%) had histologic evidence of recurrence after a median of seven months post-transplant. Nine of the 18 had no abnormal proteinuria at the time of diagnosis. Five patients had low proteinuria; just four patients had high levels.
"Tissue biopsies have helped us uncover subclinical conditions that would otherwise go unnoticed until the damage is too great and therapy is potentially not as effective," Dr. El Ters says.
Mayo Clinic's protocols also include administration of rituximab before kidney transplantation for patients with primary FSGS. Preconditioning for patients with PGNMID is being explored. Four of the 20 patients in the 2019 PGNMID study had preconditioning with rituximab. Three of them developed mild recurrent disease; none of the three grafts was lost. Dr. El Ters notes that these results are preliminary. "More data is needed to make a firm conclusion about preconditioning," she says.
Another strategy for preventing GN recurrence involves long-term prednisone treatment. Typically, transplant patients are weaned off that medication, to avoid side effects. "But there is good data to suggest that continuing prednisone long term may help lower the risk of disease recurrence in IgA nephropathy," Dr. Mai says.
When GN does recur, Mayo Clinic uses various immunosuppressive therapies to treat aggressive forms of recurrent disease such as PGNMID, FSGS and membranous nephropathy. "It's important to note that even in less aggressive disease, recognizing and treating recurrence early — sometimes just by better controlling risk factors such as hypertension, hyperlipidemia, obesity and diabetes — can help prolong the life of the allograft," Dr. El Ters says.
Although certain forms of glomerular diseases can have a high rate of recurrence, Mayo Clinic works to manage that risk. "Our protocols are a key factor in our success with tackling this problem," Dr. Khamash says. "Having GN — including one of the forms with a high recurrence rate — does not rule out receiving a kidney transplant if active surveillance is provided post-transplant and, in some cases, pretransplant conditioning therapy is considered."
For more information
Transplant Center. Mayo Clinic.
Buxeda A, et al. Recurrent proliferative glomerulonephritis with monoclonal immunoglobulin deposits in kidney allografts treated with anti-CD20 antibodies. Transplantation. 2019;103:1477.