C3 glomerulonephritis (C3GN) results from abnormalities in the alternative pathway of complement, and it is characterized by deposition of C3 with absent or scant Ig deposition. In many patients, C3GN progresses to ESRD. The clinical features, pathology, and outcomes of patients with C3GN receiving kidney transplantation are unknown. Between 1996 and 2010, we identified 21 patients at our institution who received a kidney transplant because of ESRD from C3GN. The median age at the time of initial diagnosis of C3GN at kidney biopsy was 20.8 years. The median time from native kidney biopsy to dialysis or transplantation was 42.3 months. Of 21 patients, 14 (66.7%) patients developed recurrent C3GN in the allograft. The median time to recurrence of disease was 28 months. Graft failure occurred in 50% of patients with recurrent C3GN, with a median time of 77 months to graft failure post-transplantation. The remaining 50% of patients had functioning grafts, with a median follow-up of 73.9 months. The majority of patients had hematuria and proteinuria at time of recurrence. Three (21%) patients were positive for monoclonal gammopathy and had a faster rate of recurrence and graft loss. Kidney biopsy at the time of recurrence showed mesangial proliferative GN in eight patients and membranoproliferative GN in six patients. All allograft kidney biopsies showed bright C3 staining (2-3+), with six biopsies also showing trace/1+ staining for IgM and/or IgG. To summarize, C3GN recurs in 66.7% of patients, and one half of the patients experience graft failure caused by recurrence.

On examination of the records of 1321 patients following kidney transplant over an 11-year period, we found that 29 patients had recurrent membranoproliferative glomerulonephritis (MPGN). We excluded from this analysis patients who had MPGN type II, those with clear evidence of secondary MPGN, and those lacking post-transplant biopsies. During an average of 53 months of follow-up, we found using protocol biopsies that 12 of these patients had recurrent MPGN diagnosed 1 week to 14 months post-transplant. In 4 of the 12 patients this presented clinically, whereas the remaining had subclinical disease. The risk of recurrence was significantly increased in patients with low complement levels. Serum monoclonal proteins were found in a total of six patients; appeared to be associated with earlier, more aggressive disease; and were more common in recurrent than non-recurrent disease. The recurrence of MPGN was marginally higher in recipients of living-donor kidneys. Some patients developed characteristic lesions within 2 months post-transplant, whereas others presented with minimal, atypical histological changes that progressed to MPGN. Of 29 patients, 5 lost their allograft and 2 patients remain on chronic plasmapheresis. Our study shows the risk of MPGN recurrence and progression depends on identifiable pretransplant characteristics, has variable clinical impact, and can result in graft failure.

Recent reports suggest that deep hematologic responses to chemotherapy are associated with improved renal outcomes in monoclonal immunoglobulin deposition disease (MIDD). Here we describe the long term outcomes and identify prognostic factors after first line treatment of the largest reported series of patients with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen at Mayo Clinic, MN. Renal responses were defined using criteria used for light chain amyloidosis (AL) or those used by the IMWG. Sixty-one (69%) patients had a GFR < 30 mL/min/1.73 m and 16 (18%) were on renal replacement therapy at diagnosis. The interval between albuminuria or elevation in creatinine and MIDD diagnosis was 12 months suggesting a delay in diagnosis. Thirty-seven patients (42%) had at least a hematologic CR/VGPR. Fifty-three (60%) received an autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)-based treatments. Patients receiving ASCT or PI-based therapies were more likely to achieve at least a hematologic CR/VGPR compared to those receiving other therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year overall and renal survival for the entire cohort was 67% and 57%, respectively. In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m and a renal response (using AL or IMWG criteria) were independently predictive of progression to dialysis. This study confirms that deep hematologic responses, best achieved with ASCT or PI-based therapies, are a prerequisite to achieving renal responses. Am. J. Hematol. 91:1123-1128, 2016. © 2016 Wiley Periodicals, Inc.

About 70% of patients with primary membranous nephropathy (MN) have circulating anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease activity, but their predictive value in post-transplant (Tx) recurrent MN is uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without recurrence, with serial post-Tx serum samples and renal biopsies to determine if patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared to seronegative patients and to determine if post-Tx changes in anti-PLA2R correspond to the clinical course. In the recurrent group, 10/17 patients had anti-PLA2R at the time of Tx vs. 2/7 patients in the non-recurrent group. The positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the negative predictive value was 42%. Persistence or reappearance of post-Tx anti-PLA2R was associated with increasing proteinuria and resistant disease in many cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and biopsy evidence of recurrence in which the antibodies resolved with standard immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative at the time of recurrence. In conclusion, patients with positive pre-Tx anti-PLA2R should be monitored closely for recurrent MN. Persistence or reappearance of antibody post-Tx may indicate a more resistant disease.

Background and objectives: Management of incidental renal artery and kidney abnormalities in patients undergoing computed tomography scans is a clinical challenge because their frequency in healthy subjects has not been precisely estimated. Therefore, the prevalence and management of these abnormalities were determined among a large cohort of potential kidney donors undergoing protocol evaluations.Design, setting, participants, & measurements: All patients at the Mayo Clinic who underwent computed tomographic angiography and urography as part of their kidney donor evaluation between 2000 and 2008 were identified. Radiographic reports were abstracted for abnormalities of the renal arteries and kidneys. The prevalence of radiographic abnormalities was stratified by age and gender, and the effect on approval for kidney donation was determined.Results: Among 1957 potential kidney donors, the mean ؎ SD age was 43 ؎ 12 years, and 58% were women. The most common abnormalities were kidney stones (11%), focal scarring (3.6%), fibromuscular dysplasia (2.8%), and other renal artery narrowing or atherosclerosis (5.3%). Fibromuscular dysplasia, focal scarring, parenchymal atrophy, and upper tract dilation were more common in women. Renal artery narrowing, focal scarring, and indeterminate masses increased with age. Overall, 25% of potential donors had at least one abnormality. However, these incidental radiographic abnormalities contributed to exclusion from donation in only 6.7% of potential donors.Conclusions: Incidental radiographic abnormalities of the renal arteries and kidneys are common. The majority of imaging findings are not perceived to be harmful enough to prevent kidney donation, but future studies are needed to determine their clinical relevance.

Membranous nephropathy recurs in 48% of cases threatening the allograft. Treatment of early but progressive recurrence with anti-CD20 antibodies is quite effective achieving clinical remission and histologic resolution of MN.

ASCT may be an effective therapy for renal dysfunction associated with LCDD. In cases where kidney dysfunction persists after ASCT, a haematological response may permit successful kidney transplantation with improved graft viability and decreased risk of recurrence.

Oxalate arthropathy is a rare cause of arthritis characterized by deposition of calcium oxalate crystals within synovial fluid. This condition typically occurs in patients with underlying primary or secondary hyperoxaluria. Primary hyperoxaluria constitutes a group of genetic disorders resulting in endogenous overproduction of oxalate, whereas secondary hyperoxaluria results from gastrointestinal disorders associated with fat malabsorption and increased absorption of dietary oxalate. In both conditions oxalate crystals can deposit in the kidney leading to renal failure. Since oxalate is primarily renally eliminated, it accumulates throughout the body in renal failure, a state termed oxalosis. Affected organs can include bones, joints, heart, eyes and skin. Since patients can present with renal failure and oxalosis before the underlying diagnosis of hyperoxaluria has been made, it is important to consider hyperoxaluria in patients who present with unexplained soft tissue crystal deposition. The best treatment of oxalosis is prevention. If patients present with advanced disease, treatment of oxalate arthritis consists of symptom management and control of the underlying disease process.