Clinicopathological Spectrum and Treatment Outcomes of Cryofibrinogen-Associated Nephropathies.

INTRODUCTION

Cryofibrinogen-associated nephropathy (CFN) is a very rare disease. Only few data are available about the clinicopathological presentation and treatment outcomes.

METHODS

Patients with cryofibrinogenemia (CF) diagnosed in French expert laboratories, and kidney biopsy findings suggestive of CFN (pauci-immune membranoproliferative glomerulonephritis [MPGN], thrombotic microangiopathy [TMA] and/or indirect signs of ischemia) were retrospectively included. Estimated glomerular filtration rate (eGFR), urinary protein-to-creatinine ratio (UPCR), and specific treatments were collected. Renal response (RR) was defined as a reduction of UPCR to < 0.5 g/g (or decrease > 50% if > 3 g/g at baseline) and an improvement of eGFR > 30% (if < 60 ml/min per 1.73 m2 and acute kidney injury (AKI) at baseline).

RESULTS

Among 2545 patients with CF, 232 (9%) underwent kidney biopsy, and only 28 (1%) had histological findings suggestive of CFN. Ten patients (36%) were female, and median age was 62 (interquartile range [IQR]: 49-71) years. eGFR at diagnosis was 21 (14-44) ml/min per 1.73 m2. Median UPCR was 3.30 (IQR: 1.52-4.85) g/g. AKI (78%) and nephrotic syndrome (41%) were frequent. Nine patients had an essential form, whereas 19 had a secondary form. MPGN was the most frequent pattern, with double contours (57%), nodular mesangial sclerosis (30%), mesangial (41%), endocapillary (56%) and extracapillary (11%) hypercellularity, and interstitial immune infiltration (41%). Thrombi were found in 43% of cases. Strikingly, 58% of the secondary forms were associated with a monoclonal gammopathy (MG). Patients with MG had more frequent skin manifestations (P = 0.002), endocapillary (P = 0.002), interstitial (P = 0.041) infiltration, and capillary thrombi (P = 0.012), and tended to have more frequent complement activation (P = 0.14). Sixty percent of patients were treated with various regimens of immunosuppressants (IS). After a mean follow-up of 476 (± 92) days, 65% of patients had an RR. Higher baseline eGFR (P = 0.04) and use of IS (P = 0.03) were predictive of RR. B-cell or plasma-cell depletion was effective in most cases associated with MG (80%).

CONCLUSION

Our study, to the best of our knowledge, described for the first time the prevalence and the clinicopathological spectrum of CFN, which might be a very rare and underrecognized form of MG of renal significance presenting with pauci-immune MPGN ot TMA. IS are effective in most cases.