MO174: Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: Rare Disease with Poor Prognosis?

Abstract

Abstract BACKGROUND AND AIMS Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs) is a recently described disease among the spectrum of monoclonal gammopathy of renal significance (MGRS). The disease is renal limited and manifests with chronic glomerular disease, altered renal function and albuminuria, sometimes in the nephrotic range. Kidney injury results from direct glomerular deposition of the monoclonal immunoglobulin. Of note, in approximately 70% of the cases of PGNMID, a clone cannot be detected. METHOD Clinical case of PGNMID. RESULTS A 36-year-old woman, with a past history of acute glomerulonephritis, was treated with mycophenolate mofetil 2 g and concomitant methylprednisolone 2 mg from January 2020 to September 2021 (kidney biopsy was not performed). After 3 months, she showed recurrence of nephrotic syndrome: peripheral edema, severe weakness, shortness of breath, decreased diuresis up to oliguria and increased blood pressure. Blood analysis has shown: GFR 127 mL/min/1.73 m2, total protein 44.4 g/L, albumin 16.2 g/L; autoimmune markers—negative; kappa free light chains 182 mg/L (3.3–19.4 mg/L); lambda free light chains 112 mg/L (5.71–26.3 mg/L), ratio of kappa/lambda 1.63 (0.26 to 1.65). Urine analysis has shown: total protein excretion rate 3.5 g/24 h; albuminuria 1000 mg/g; urine microscopy—normal; kappa free light chains ++++; lambda free light chains +++. A kidney biopsy has shown up to 12 glomerulies, which have different sizes, some are enlarged, as due to diffuse proliferation of mesangial cells, oedema and segmental proliferation of endothelial cells, as fibrinoid changes; some of the capillary loops are infiltrated with monocytes, an uneven increase in the mesangial matrix, there are small areas of segmental sclerosis that tend to be nodular in some glomerulies. Degenerative changes (granular, vacuolar, in some areas hyaline-droplet dystrophy), necrosis of epithelial cell groups, areas of epithelial atrophy with thickening of the tubular basement membrane (up to 10% of the biopsy volume) are sharply expressed in the tubules. In the tubules—protein masses, exfoliated epithelium, the lumen of the tubules is sharply reduced and/or absent due to pronounced degenerative changes in the epithelium. In the stroma—edema, areas of interstitial fibrosis, including perivascular (up to 10% of the biopsy volume), focal lymphohistiocytic cell infiltrates. By definition, there is evidence of monoclonal deposits by immunofluorescence: IgA (predominantly), IgG, IgM, С3 deposits; С1q, CD20 (В- lymphocytes), AA amyloidosis -negative expression; kappa free light chains (predominantly) +++; lambda free light chains ++ (Figure 1). Finally, we reached a clinical diagnosis of CKD G1, A3: PGNMIDs (IgM, IgA, IgG; LC Ķ˃λ). Nephrotic syndrome. Light Chain Deposition Disease. At that point (January 2021), we have started clone-targeted chemotherapy following the data sheet, with urinary and haematological response after 2 weeks, and normal kidney function with complete remission of nephrotic syndrome after 4 weeks, as well as a negativization of kappa and lambda free light chains deposits (Table 1). Three months after admission, the patient maintained haematological and kidney remission up to now. CONCLUSION MGRS is not an independent kidney disease, not ‘chronic glomerulonephritis’, but a condition in which kidney damage is secondary to clonal B-cell proliferation. In other words, MGRS is a precancerous disease combined with chronic kidney disease that requires immediate treatment. Renal prognosis is poor, with progression to ESKD in 25% of patients within 30 months and frequent early recurrence on the renal allograft. However, recent studies indicate that clone-targeted chemotherapy may significantly improve renal outcomes, opening future perspectives for the management of this rare disease.