Comparison of Complement Pathway Activation in Autoimmune Glomerulonephritis.

Introduction: Studies on complement activation have implicated a combination of the classical pathway (CP), lectin pathway (LP), and alternative pathway (AP) in triggering the terminal pathway (TP) for each common autoimmune glomerulonephritis (GN). Evaluating different pathways simultaneously may help identify whether one is preferentially activated and, consequently, which is best to target for each disease. Methods: We followed 112 patients with focal segmental glomerular sclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), lupus nephritis (LN), and antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) for a median duration of 22 (12-52) months. At the time of greatest clinical activity, we simultaneously evaluated urinary C3a (C3 convertase activity), C5a and sC5b-9 (TP), MASP-1 and MASP-2 (LP), C1q (CP), C4a (CP/LP), and Ba and Bb (AP). We evaluated the relation between activation fragments of the AP and CP/LP with the TP. Results: Urinary complement biomarkers for each pathway were associated with the severity of proteinuria. Fragments of the TP were higher among patients with FSGS and MN compared with patients with IgAN, LN, and AAV. For the AP, urinary Ba level was lower in those with IgAN and LN compared with those with FSGS. For the CP/LP, urinary C4a, MASP-1, and MASP-2 levels were similar between diseases whereas urinary C1q levels were lower in those with LN. For each GN, independent associations existed between the activation markers of the AP and CP/LP with the degree of TP activation, except for the AP in AAV, although perhaps underpowered. Conclusion: The AP and CP/LP contribute individually to the TP activation in autoimmune GN, and both seem to be valid potential therapeutic targets.

Kidney function before pancreas transplant alone predicts subsequent risk of end-stage renal disease.

BACKGROUND: Recipients of a pancreas transplant alone (PTA) have varying levels of kidney function at the time of transplantation, but the role of kidney function in predicting the risk of end-stage renal disease (ESRD) after PTA remains unclear. METHODS: A study was conducted on 1,135 adult recipients of a first PTA from January 1, 1994 to December 31, 2009 in the Scientific Registry of Transplant Recipients. ESRD events were derived from the United States Renal Data System. Cox proportional hazards models were fitted to determine the independent association of the estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration formula before PTA and ESRD. The continuous relation between eGFR and ESRD was modeled using fractional polynomial terms. RESULTS: The cumulative probabilities of ESRD for eGFR ≥ 90, 60 to 89.9, and <60 mL/min/1.73 m(2) at 5 years were 3.5, 12.2, and 26.0%, and at 10 years were 21.8, 29.9, and 52.2%, respectively. Patients with eGFR <60 and 60 to 89.9 mL/min/1.73 m(2) were 7.74 (95% CI: 4.37, 13.74) and 3.25 (95% CI: 1.77, 5.97) times more likely to develop ESRD than patients with eGFR ≥ 90 mL/min/1.73 m(2). The fractional polynomial model showed a log-linear relation between eGFR and the hazard ratio for ESRD. The results were robust to several sensitivity analyses. CONCLUSIONS: Kidney function before PTA is a strong independent predictor of ESRD. These results may inform patient selection and the use of targeted interventions to reduce the risk of progressive kidney impairment in this patient population.

Impact of early graft function on 10-year graft survival in recipients of kidneys from standard- or expanded-criteria donors.

BACKGROUND: The use of kidneys from expanded-criteria donors (ECD) is regarded with caution. METHODS: We compared 279 kidney transplant recipients (KTxR) from standard-criteria donors (SCD) and 237 from ECD, transplanted between January 1990 and December 2006. We evaluated the impact of immediate graft function (IGF), slow graft function (SGF), and delayed graft function (DGF) and the drop in estimated glomerular filtration rate (ΔeGFR) ≤ 30% or > 30% during the first year after transplantation on long-term patient and death-censored graft survival (DCGS). RESULTS: Ten-year patient survival was similar in SCD- or ECD-KTxR (P = 0.38). DCGS was better in SCD-KTxR versus ECD-KTxR (77.3% vs. 67.3%; P = 0.01). DCGS did not differ in either group experiencing IGF (P = 0.17) or DGF (P = 0.12). However, DCGS was worse in ECD-KTxR experiencing SGF (84.9% vs. 73.7%; P = 0.04). Predictors of DCGS were 1-year serum creatinine (hazard ratio, 1.03; P < 0.0001) and ΔeGFR > 30% between 1 and 12 months (Δ1-12eGFR) after transplantation (hazard ratio, 2.2; P = 0.02). In ECD-KTxR with IGF and more than 1-year follow-up, 10-year DCGS was better in those with Δ1-12eGFR ≤ 30% versus those with Δ1-12eGFR > 30% (83.8% vs. 53.6%; P = 0.01). CONCLUSION: Recipients of SCD or ECD kidneys with IGF or DGF had similar 10-year patient survival and DCGS. SGF had a worse impact on DCGS in ECD-KTxR. In addition to 1-year serum creatinine, Δ1-12eGFR > 30% is a negative predictor of DCGS. Larger studies should confirm if increasing the use of ECD, avoiding factors that contribute to SGF or DGF, and/or a decline in eGFR during the first year after transplantation may expand the donor pool and result in acceptable long-term outcomes.

Renal function in recipients of pancreas transplant alone.

PURPOSE OF REVIEW: Pancreas transplant alone (PTA) has become an accepted therapy for selected nonuremic patients with type 1 diabetes mellitus. We report a literature review, as well as data from the McGill University pancreas transplant program. RECENT FINDINGS: The published literature suggests that there is reversibility of diabetic nephropathy when normoglycemia is maintained for 5-10 years after successful PTA. There is also evidence of development and progression of histological lesions compatible with calcineurin inhibitor nephrotoxicity, as well as a decline in renal function overtime, with an increased risk of end-stage renal disease (ESRD). We studied 43 patients with PTA. Nine patients had a pretransplant estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m, and 34 patients had an eGFR greater than 60 ml/min/1.73 m. The actuarial incidence of ESRD at 1, 3 and 5 years was 0, 28.57 and 61.9% in patients with pretransplant eGFR less than 60 ml/min/1.73 m, and 0, 8.2 and 12.5% in patients with pretransplant eGFR greater than 60 ml/min/1.73 m, respectively (P=0.006). Multivariate analysis confirmed that age, sex, duration of diabetes prior to PTA and eGFR pretransplant were significant predictors of ESRD. SUMMARY: The ideal management of candidates for PTA with eGFR less than 60 ml/min/1.73 m remains to be determined. Future studies should focus on determining potentially reversible predictive factors of progression to ESRD after PTA, as well as the outcomes of these patients on chronic dialysis.