Key Points: Fifty-five percent of patients achieve long-term remission after rituximab treatment. This is influenced by maintenance therapy with rituximab. A substantial reduction of annualized relapse rate and concomitant immunosuppression was observed after rituximab treatment. Background: Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or FSGS) are largely unknown. Methods: A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months. Results: One hundred eighty-three adult patients (n=64 with FSGS and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over 3 years. Maintenance therapy with rituximab was associated with a better relapse-free survival (hazard ratio, 2.05; 95% confidence interval [CI], 1.07 to 3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared with 36% of patients without maintenance treatment (odds ratio, 2.69; 95% CI, 1.27 to 5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI, 1.0 to 1.7) before to 0.17 (95% CI, 0.00 to 0.24) relapses per year after rituximab initiation. Over the 36 months of follow-up, a stable course of eGFR was observed in those who initially responded with either complete or partial remission, whereas nonresponders experienced a reduction in eGFR reaching −11 (95% CI, −18 to −8) ml/min per 1.73 m². Conclusions: Rituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab was further associated with long-term relapse-free survival over 3 years. Nonresponse to initial rituximab treatment was associated with poor kidney prognosis.

Background: Nephrotic syndrome (NS) is associated with a hypercatabolic state expressed as an exacerbated degradation of muscle mass. However, the clinical significance of this phenomenon has not yet been investigated.The aim of the study was to evaluate the nutritional status of patients with severe NS (defined as nephrotic range proteinuria with hypoalbuminemia ≤2.5 g/dL) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m²in comparison to patients in different stages of chronic kidney disease (CKD).Methods: Twenty men with severe NS (NS group) and 40 men without proteinuria similar in term of serum creatinine (control group) were included into the study. A retrospective cohort of 40 men with CKD stage G4 (PreD group) and 20 haemodialysis men (HD group) were added to the analysis after matching for age, height and weight using propensity score matching. The bioimpedance spectroscopy and biochemical nutritional markers were evaluated.Results: Nephrotic patients had a significantly lower lean tissue mass (LTM;p = 0.035) and index (a quotient of LTM over height squared, LTI;p = 0.068), with an expected deficiency of LTM by 3.2 kg, and LTI by 0.9 kg/m²when compared to the control group. A significant lean tissue deficit (defined as LTI below the lower limit of the reference range by 1.0 kg/m²) was observed in 12.5% of patients in the control group in comparison to 31.7% with advanced CKD (PreD+HD;p = 0.032) and 50% with NS (p = 0.003). NS group presented with higher phosphorus (p = 0.029), uric acid (p = 0.002) and blood urea (p = 0.049) than the control group. Blood urea was strongly negatively correlated with LTM in NS (r = − 0.64,p = 0.002). Nine nephrotic patients (45%) were identified as hypercatabolic based on severe hyperphosphatemia (> 5.0 mg/dL) and/or hyperuricemia (> 8.0 mg/dL), and were characterized by higher blood urea and lower prealbumin, as well as LTM lower by 5.6 kg than in less catabolic individuals.Conclusions: In term of lean tissue amount, NS group was more similar to advanced CKD than to the control group. We concluded that specific metabolic pattern with elevated phosphorus, uric acid and blood urea, and lean tissue deficiency may be defined as protein-energy wasting associated with nephrotic syndrome (neph-PEW).

Testosterone deficiency is a common disorder among men treated with hemodialysis. The aim of our study was to evaluate the relationship between free testosterone levels and body composition, biochemical markers of nutritional status, and inflammation in men on hemodialysis. Prospective analysis of men treated with hemodialysis for more than 3 months in one hemodialysis center. A total of 56 men—41 men undergoing hemodialysis treatment thrice-weekly over a period of at least 3 months (HD group) and 15 men without kidney disease, with estimated glomerular filtration rate >60 mL/min/1.73 m² (C group)—were included. Serum levels of free testosterone, creatinine, protein, albumin, prealbumin, high-sensitivity C-reactive protein, and interleukin 6 and body composition by bioimpedance spectroscopy, waist-to-hip ratio, and waist-to-height ratio were measured. None, observational study. Free testosterone level. The mean free testosterone level was significantly lower in the HD group than that in the C group and positively correlated with lean tissue index (LTI, r = 0.51, P = .001) and body cell mass (BCM, r = 0.57, P < .001). Significant, negative correlations were observed between free testosterone level and age (r = −0.4, P = .004) as well as fat tissue index (r = −0.36, P = .018). In a subgroup of men on hemodialysis who have low testosterone levels (<9.4 pg/mL), we observed a lower LTI and BCM and higher age, fat tissue index, and loginterleukin-6. In our receiver operating characteristic curve analysis, LTI and BCM were shown to be good predictors of a low testosterone level with cutoff points of 13.3 kg/m² and 22.3 kg, respectively, meaning that men on hemodialysis with LTI <13.3 kg/m² were 26 times more likely to have free testosterone levels below 9.4 pg/mL (odds ratio, 26.7; 95% confidence interval: 3.0-236.6). Low lean tissue mass and BCM can be predictors of low testosterone level.

Severe nephrotic syndrome (NS) is associated with high risk of venous thromboembolic events (VTE), as well as presumably altered heparin pharmacokinetics and pharmacodynamics. Although prophylactic anticoagulation is recommended, the optimal dose is not established. The aim of the study was to test two co-primary hypotheses: of reduced enoxaparin effectiveness and of the need for dose-adjustment in NS. Forty two nephrotic patients with serum albumin ≤2.5 g/dL were alternately assigned to a standard fixed-dose of enoxaparin (NS-FD: 40 mg/day) or ideal body weight (IBW)-based adjusted-dose (NS-AD: 1 mg/kg/day). Twenty one matched non-proteinuric individuals (C-FD) also received fixed-dose. Co-primary outcomes were: the achievement of low- and high-VTE risk threshold of antifactor-Xa activity (anti-FXa) defined as 0.2 IU/mL and 0.3 IU/mL, respectively. Low-VTE-risk threshold was achieved less often in NS-FD than C-FD group (91 vs. 62%, p = 0.024), while the high-VTE-risk threshold more often in NS-AD than in NS-FD group (90 vs. 38%, p < 0.001). Two VTE were observed in NS during 12 months of follow-up (incidence: 5.88%/year). In both cases anti-FXa were 0.3 IU/mL implying the use of anti-FXa >0.3 IU/mL as a target for dose-adjustment logistic regression models. We determined the optimal dose/IBW cut-off value at 0.8 mg/kg and further developed bivariate model (termed the DoAT model) including dose/IBW and antithrombin activity that improved the diagnostic accuracy (AUC 0.85 ± 0.06 vs. AUC 0.75 ± 0.08). Enoxaparin efficacy is reduced in severe NS and the dose should be adjusted to ideal body weight to achieve target anti-FXa activity.

Case Presentation A 35-year-old woman without past medical history sought treatment for fatigue and dry cough of 3 weeks’ duration. Basic laboratory tests revealed severe anemia. She had no history of bleeding, hemoptysis, dyspnea, or fever. The patient was admitted for RBC transfusion and more extensive diagnostics.