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Serum immunoglobulin G level in patients with lupus nephritis and the effect of treatment with corticosteroids and mycophenolate mofetil

Background Reduced serum IgG level is associated with increased risk of infection. We investigated the circulating IgG level and its determining factors in active lupus nephritis patients treated with corticosteroids and mycophenolate mofetil (MMF). Methods This was a retrospective study on the longitudinal IgG profile in Class III/IV ± V lupus nephritis patients treated with prednisolone and MMF. Results 46 patients were included. At baseline, 34 (73.9%) patients (Group I) had normal or elevated IgG (1444.0 ± 600.5 mg/dL) while 12 (26.1%) (Group II) had IgG levels (567.8 ± 160.9 mg/dL) below the lower limit of normal. IgG levels at baseline, three, six and 12 months after treatment were 1215.4 ± 649.7 mg/dL, 843.9 ± 347.6 mg/dL, 914.5 ± 362.4 mg/dL and 1034.6 ± 452.5 mg/dL respectively. Treatment with prednisolone and MMF led to a significant drop in IgG after two weeks, reaching a nadir at eight weeks, followed by gradual normalization. Similar changes in IgG were observed in Group I patients but there was non-significant change in Group II within the first 24 weeks. Eighteen (39.1%) patients had low IgG by six months, and only one patient had IgG <300 mg/dL, at both three and six months. IgG level was negatively associated with proteinuria at six months (r = −0.711, p = 0.010). Five of 18 patients with low IgG had infections within the first year, while IgG levels below the lower limit of normal did not increase infection risk (relative risk 1.863; 95% confidence interval 0.466 to 6.818, p = 0.280). Conclusion Reduced IgG occurred in 26% of active lupus nephritis patients and the IgG levels are significantly influenced by the severity of proteinuria. Treatment with prednisolone and MMF does not result in clinically important suppression of IgG.

427 Relapse of lupus nephritis – risk factors and impact of mycophenolate treatment

Background and aims The management of lupus nephritis (LN) has evolved over time. There is limited data on renal flares in the recent era. Methods We investigated the renal relapse rate in 139 patients with a history of Class III/IV±V diagnosed during the period of Jan 1983 to Dec 2013, and the factors associated with renal flares. Results 135 episodes of renal relapse occurred over 112.5±88.4 months, giving a flare rate of 0.108 episode per patient-year. Reduced risk of renal flare was associated with maintenance treatment using mycophenolate (MPA) (OR 0.314, 95% CI 0.099–0.994, p=0.049), complete remission after the prior episode of active LN (OR 0.329, 95% CI 0.133–0.810, p=0.016), and diagnosis of LN after 1998 (OR 0.305, 95% CI 0.133–0.700, p=0.005) when maintenance therapy with MPA was instituted. Low-dose prednisolone and MPA maintenance immunosuppression was associated with better relapse-free survival (5 year 91% and 10 year 83%) than prednisolone and azathioprine (AZA) (70% and 52% respectively, p=0.044) (Figure 1). LN diagnosed in 1998–2013 was associated with 5 year and 10 year relapse-free survival rates of 93% and 86% respectively, compared with 81% and 66% respectively (p=0.017) for patients who presented in 1983–1997 (Figure 2). Abstract 427 Figure 1 Abstract 427 Figure 2 Conclusions The risk of renal relapse has decreased in the current era, probably attributed to replacement of AZA with MPA as maintenance treatment.

109 Long-term data on sirolimus treatment in lupus nephritis patients

Background and aims Preliminary data suggested efficacy of sirolimus in treatment of lupus nephritis (LN), but its long-term efficacy and tolerability data is lacking. Methods We reviewed Class III/IV/V LN patients who received prednisolone and sirolimus either as initial or maintenance treatment during Jan 2007 to Jan 2016. Results Sixteen patients were included (duration of sirolimus treatment: 27.2±19.6 months). Ten patients received sirolimus due to intolerance to standard immunosuppressive treatments and six patients because of a history of malignancy. Five patients received sirolimus during active LN, and showed improvement in proteinuria (2.8±1.9 g/day and 0.1±0.1 g/day at baseline and 36 months, p=0.011 compared to baseline), anti-dsDNA (107.7±91.9 IU/mL and 37.0±55.4 IU/mL at baseline and 36 months, p=0.145) and C3 (54.8±26.1 mg/dL and 86.3±18.6 mg/dL at baseline and 36 months, p=0.084). Eleven patients received sirolimus during disease quiescence, and showed significant improvement in C3 (90.4±18.1 mg/dL and 117.7±25.1 mg/dL at baseline and 36 months, p=0.025) and stable renal function (58.5±25.2 ml/min and 56.7±29.0 mL/min at baseline and 36 months, p=0.199) and proteinuria (0.8±0.7 g/day and 0.7±0.7 g/day at baseline and 36 months, p=0.263). One patient, whose serum creatinine was 244 µmol/L when sirolimus was started, developed renal failure after 27 months. Renal flare occurred in one patient after 36 months. Sirolimus was discontinued in five patients including one with leucopenia. Four patients showed lipid profile deterioration which was adequately controlled with statin. Conclusions Sirolimus can be an alternative treatment option for LN and the long-term results do not suggest excessive adverse effects.

428 Pre-emptive treatment for asymptomatic serological reactivation in lupus nephritis patients – impact on clinical flare rate and renal function

Background and aims Pre-emptive immunosuppressive treatment for asymptomatic serological activation (ASR) in lupus nephritis (LN) patients remains controversial, and its impact on subsequent flare rate and long-term renal outcome is unclear. Methods We conducted a retrospective study on all episodes of ASR in 1993–2015 to investigate the relationship between pre-emptive treatment and subsequent clinical flares and renal outcomes. Results 138 episodes of ASR occurred in 98 patients during the study period. 53 episodes (in 38 patients) were treated with pre-emptive increase in immunosuppression while 85 episodes (in 60 patients) were not, and patients were followed up for 88.8±77.3 months and 82.8±89.7 months respectively after ASR occurred. Pre-emptive treatment was associated with superior renal relapse-free survival (100%, 95% and 90% at 6, 12 and 24 months respectively) compared with no pre-emptive treatment (93%, 68% and 65% respectively, p=0.007), while extra-renal relapse-free survival did not differ between the two groups (Figure 1). 5 (9.4%) of 53 ASR episodes treated pre-emptively developed renal flare at 14.3±6.7 months after ASR. Patients who received pre-emptive treatment for ASR and did not develop renal flares showed also better eGFR slope (+0.54±0.43 ml/min/1.73 m2/year) compared with the non-pre-emptive groups with or without renal flares (−2.11±0.50 and −1.00±0.33 ml/min/1.73 m2/year respectively, p=0.001 and 0.012) (Figure 2). Pre-emptive treatment was associated with more gastrointestinal adverse events related to increased mycophenolate dose (p=0.031). Infection rate was similar between both groups. Abstract 428 Figure 1 Abstract 428 Figure 2 Conclusions Renal flares have a negative impact on renal function and pre-emptive treatment for ASR could reduce renal flare risk and its consequences in LN patients.

Peritoneal Dialysis-Related Peritonitis Caused by Erosion of Umbilical Abscess into the Peritoneal Cavity

access and all-cause mortality: a propensity score analysis. J Am Soc Nephrol 2004; 15:477–86. 3. Brown PA, McCormick BB, Knoll G, Su Y, Doucette S, Fergusson D, et al. Complications and catheter survival with prolonged embedding of peritoneal dialysis catheters. Nephrol Dial Transplant 2008; 23:2299–303. 4. McCormick BB, Brown PA, Knoll G, Yelle JD, Page D, Biyani M, et al. Use of the embedded peritoneal dialysis catheter: experience and results from a North American Center. Kidney Int Suppl 2006; (103):S38–43. 5. Rambausek M, Zeier M, Weinreich T, Ritz E, Rau J, Pomer S. Bowel perforation with unused Tenckhoff catheters. Perit Dial Int 1989; 9:82. 6. Brady HR, Abraham G, Oreopoulos DG, Cardella CJ. Bowel erosion due to dormant peritoneal catheter in immunosuppressed renal transplant recipients. Perit Dial Int 1988; 8:163–5. doi:10.3747/pdi.2011.00016

Staphylococcus aureus Peritonitis in Two Peritoneal Dialysis Patients: An Uncommon Complication of Peripheral Intravenous Catheter Infection

Our patient was treated successfully on PD for 20 years, without worsening of peritoneal function. An earlier study has demonstrated that patients are able to survive a long time on PD when they are nondiabetic and have few comorbid conditions (2). Those findings are consistent with our patient’s situation. Combination PD+HD might have played a role in his favorable result. Combination therapy has been used as an alternative to an increase in the dose of dialysis in PD patients with declining residual renal function (3). In 2009, 19% of Japanese patients treated with PD alone had a dialysis vintage of more than 5 years (4). About one fifth of PD patients are treated with PD+HD, and the ratio of combination therapy with HD increases with prolonged PD duration (4). Combined therapy improves volume status and solute removal (3). We recently reported an additional beneficial effect on left ventricular hypertrophy (5). In addition, PD+HD may also permit a “PD holiday” with peritoneal rest, which can improve quality of life and might be effective in preserving peritoneal function and preventing encapsulating peritoneal sclerosis (3). In fact, an analysis demonstrated improvements in peritoneal function after a switch to PD+HD from daily PD (6). Combination therapy may permit the safe prolongation of PD after loss of residual renal function, although further studies are necessary to clarify the issue.

Causes of death in patients with severe lupus nephritis

Introduction: Angiotensin II (AT II) plays a important role in the development of proteinuria not only by hemodynamic but also pathologic effects. As the podocyte is a main component in glomerular fi ltration units, we investigated the effect of AT II on the quantitative and qualitative changes of podocyte cytoskeletal proteins. Methods: Cultured podocytes were treated with various concentrations of AT II and losartan, a AT II type 1 receptor blocker. The quantitative changes of podocyte cytoskeletal proteins including α-actinin, synaptopodin, and I-plastin were analyzed by Western blotting (WB) and RT-PCR and the qualitative distributional changes were observed by confocal microscopy. Results: AT II decreased the amount of these three cytoskeletal proteins in WB signifi cantly in a dose-dependent manner, which were reversed by losartan. However, mRNA expressions of cytoskeletal proteins by RT-PCR were unremarkable. In confocal imaging, these three cytoskeletal proteins were co-localized. AT II changed the distribution of α-actinin from peripheral to inner cytoplasm and those of synaptopodin and I-plastin into concentrated in dosedependent manner, which were also attenuated by losartan. Conclusion: AT II modulates the phenotypes of podocyte cytoskeletal proteins via AT II type 1 receptor, therefore, may induce pathologic changes of podocytes, resulting proteinuria. *This research work was supported by the organizing committee of APCN2010.