Low-dose corticosteroid and mycophenolate for primary treatment of minimal change disease.

BACKGROUND: Mycophenolate has been shown to be effective in glomerular disease. However, the role of mycophenolate in the first-line treatment of adult-onset idiopathic minimal change disease (MCD) has not been systematically studied in a randomized fashion. AIM: To evaluate the therapeutic efficacy of enteric-coated mycophenolate sodium combined with low-dose corticosteroid as first-line treatment for MCNS. DESIGN: A prospective, open-label, randomized clinical trial. METHODS: Twenty adult patients with biopsy proven MCD were recruited and randomly assigned to receive either enteric-coated Mycophenolate Sodium (EC-MPS) plus low-dose prednisolone (Group 1: Prednisolone 0.25 mg/kg/day, n = 10) or standard-dose prednisolone (Group 2: Prednisolone 1 mg/kg/day, n = 10). RESULTS: After 24 weeks of therapy, eight patients in Group 1 vs. seven of patients in Group 2 achieved complete remission (P = 0.606). Both groups showed a significant reduction of urine protein excretion (P < 0.05) and increased serum albumin (P < 0.001) vs. baseline levels. However, no significant between-group differences were demonstrated. The relapse rate was also similar in both groups. Both treatment regimens were well tolerated but there were more patient reported adverse effects in the standard-dose prednisolone group. CONCLUSION: EC-MPS plus low-dose prednisolone is non-inferior to standard-dose prednisolone therapy in inducing clinical remission and preventing relapse in adult-onset idiopathic MCD and is associated with better tolerability and less adverse effects. This trial is registered with the ClinicalTrials.gov number NCT01185197.

Antiphospholipid antibodies in patients with lupus nephritis: clinical correlations and associations with long-term outcomes.

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000-2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-ß2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (-1.44 mL/min/year compared to -0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.

Serum level of proximal renal tubular epithelial cell-binding immunoglobulin G in patients with lupus nephritis.

In vitro data showed that immunoglobulin G (IgG) from lupus nephritis (LN) patients could bind to proximal renal tubular epithelial cells (PTEC), but the clinical relevance of such binding remained unclear. Binding of IgG and subclasses to PTEC was measured by cellular ELISA (expressed as OD index) in 189 serial serum samples from 23 Class III/IV ± V LN patients who had repeated renal flares (48 during renal flares, 141 during low level disease activity (LLDA)), and compared with 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals. Total IgG PTEC-binding index was 0.34 ± 0.16, 0.29 ± 0.16, 0.62 ± 0.27 and 0.83 ± 0.38 in healthy controls, NLGD, LN patients during LLDA, and LN patients during nephritic flare, respectively (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). PTEC-binding index for IgG1 was 0.09 ± 0.05, 0.16 ± 0.12, 0.44 ± 0.34 and 0.71 ± 0.46 for the corresponding groups (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). Sixteen of 48 episodes (33.3%) of nephritic flare showed persistent PTEC-binding IgG seropositivity for more than 9.4 ± 3.1 months, despite clinical response to immunosuppressive treatment. Total IgG and IgG1 PTEC-binding correlated with anti-dsDNA level (r = 0.34 and 0.52, respectively, p < 0.001 for both), and inversely with C3 level (r = -0.26 and -0.50, respectively, p = 0.002 and<0.001). Sensitivity/specificity of PTEC-binding index in detecting renal flares was 45.8%/80.1% for total IgG (ROC AUC 0.630, p = 0.007) and 87.5%/35.5% for IgG1 (ROC AUC 0.615, p = 0.018). IgG1 PTEC-binding index correlated with tubulo-interstitial inflammation score in renal biopsy from corresponding patients. Our data suggested that total IgG and IgG1 PTEC-binding index in serum of LN patients correlate with serological activity, and in combination could predict renal flares. The correlation between IgG1 PTEC-binding and tubulo-interstitial inflammation suggests potential pathogenetic significance.

Progressive outer retinal necrosis in a renal transplant recipient: a rare treatment success.

Renal transplant recipients (RTRs) are subject to a variety of opportunistic infections. We present a rare case of varicella zoster virus-derived progressive outer retinal necrosis in an RTR, who presented with painless visual blurring. This clinical entity heralds an extremely poor visual prognosis and is an important condition to consider in any immunocompromised host. Early diagnosis by aqueous fluid sampling and immediate institution of combined systemic and intravitreal antiviral therapy was successful in this individual.

Hydralazine-induced toxic epidermal necrolysis in a patient on continuous ambulatory peritoneal dialysis.

WHAT IS KNOWN AND OBJECTIVE: Hydralazine is an effective antihypertensive drug which acts by vasodilatation. It is well known to cause drug-induced lupus erythematosus. Nevertheless, the overall safety profile is good and cutaneous adverse effects are uncommon. To the best of our knowledge, hydralazine has never been reported to cause Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). CASE SUMMARY: We herein report the first case of hydralazine-induced TEN in a patient with end-staged renal failure. Despite meticulous wound management and intensive medical care, the patient died of a sudden cardiac arrest on day 10 of admission. WHAT IS NEW AND CONCLUSION: We speculate that patients with renal failure may be predisposed to a higher risk of allergy to drug entities that are rarely associated. Physicians should be aware that hydralazine can be a potential cause for severe allergic reaction such as SJS or TEN, particularly in the setting of poor renal excretory function. Patient education and cautious monitoring by physicians are essential for early diagnosis and hence successful management of the life-threatening condition.

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.

Prevalence and associated comorbidities of moderate to severe chronic renal impairment in Chinese nursing home older adults.

OBJECTIVE: To investigate the prevalence and associated comorbidities of Stage 3 (GFR 30-59 mL/min/1.73m(2)) and Stages 4 and 5 (GFR <30 mL/min/1.73m(2)) chronic kidney disease (CKD) among Chinese nursing home older adults. DESIGN: Retrospective cross-sectional study. Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease Study (Chinese-adjusted) equation and The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. SETTING: Nine nursing homes in Hong Kong PARTICIPANTS: Participants included 812 nursing home older adults (271 men and 571 women), mean age 86.0 ± 7.6. MEASUREMENTS: Prevalence of Stage 3 (GFR 30-59 mL/min/1.73m(2)) and Stages 4 and 5 (GFR <30 mL/min/1.73m(2)) CKD. The comorbidities associated with renal impairment were also assessed. RESULTS: There were 18.4% of nursing home older adults who had elevated serum creatinine levels above the normal limits. Using Modification of Diet in Renal Disease Study and CKD-EPI equations, 26.4% and 21.2% of them had Stage 3 CKD, whereas 6.8% and 4.4% had Stage 4-5 CKD, respectively. Diabetes mellitus, hypertension, congestive heart failure, and ischemic heart disease correlated significantly with moderate to severe renal impairment in Chinese nursing home older adults. CONCLUSION: Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients facilitates drug prescription, renal management, and advance care planning.

Superior mesenteric artery syndrome complicating dialysis patients with peritoneal failure--report of 3 cases.

We report 3 cases of superior mesenteric artery syndrome in patients previously on maintenance peritoneal dialysis converted to hemodialysis after peritoneal failure. All 3 patients presented with repeated vomiting and severe malnutrition. It is postulated that complications arising from peritoneal dialysis such as peritoneal sclerosis, adhesions and collections after CAPD peritonitis may be important contributing factors for the SMA syndrome in these 3 patients. All of them succumbed within six months of diagnosis. The first 2 patients received gastrointestinal bypass surgery and died post-operatively due to impaired wound healing and nosocomial sepsis. The 3rd patient was treated conservatively with nasoduodenal feeding but succumbed to aspiration pneumonia. It is postulated that complications arising from peritoneal dialysis including peritoneal sclerosis, adhesions and collections after CAPD peritonitis may contribute to the SMA syndrome in these patients. Our experience suggests that SMA syndrome in end-stage renal disease patients is associated with high surgical morbidity and mortality possibly related to their poor pre-morbid condition and pre-existing malnutrition. Aggressive parenteral nutrition should be considered to build up the general status before proceeding to surgical intervention.

Influences of parenchymal tethering on the reopening of closed pulmonary airways.

We investigated the influence of parenchymal tethering on the reopening of collapsed pulmonary airways. Reopening experiments were performed with freshly excised canine lobes placed in a vacuum chamber with pleural pressure (Ppl) set by vacuum pressure. Noncartilaginous 2- to 3-mm airways were collapsed by suction and remained collapsed on subsequent atmospheric pressure equalization. The airway was reopened by constant-flow insufflation, and peak pressure (Ppeak) needed to reopen the collapsed airway was measured. Yield pressure needed to begin axial meniscus motion decreased markedly at Ppl = -7.5 cmH2O, indicating a possible change in airway-meniscus configuration from compliant collapse to meniscus occlusion, thus promoting onset of reopening. Two distinct types of reopening behavior were observed: unstable low-frequency fluttering phenomenon characteristic of small magnitudes of Ppl in which airway tended to recollapse after being reopened and stable reopening phenomena at larger magnitudes of Ppl in which airway remained patent after it was reopened. Stable reopening was always observed at Ppl < or = -7.0 cmH2O. Effective transmural pressure (=Ppeak - Ppl) required to reopen airway and subsequent postreopening airway pressure, reflecting airway and collateral resistance, decreased with increasing magnitudes of Ppl due to increased influence of parenchymal tethering. However, at Ppl < -8.0 cmH2O, an increase in lung volume did not result in a reduction of effective transmural pressure, possibly indicating full airway distension and influence of airway wall hoop stress.