Introduction: Lupus nephritis (LN) affects nearly 60% of patients with systemic lupus erythematosus and up to 30% of them will progress to end-stage renal disease (ESRD), despite receiving aggressive immunosuppressive therapy. The prognostic value of ISN/RPS classification is controversial. Therefore, we aimed to identify clinical and pathological predictors of outcome in LN patients independent of this classification. Material and methods: Thirty-seven patients with LN who underwent percutaneous kidney biopsy between 1997 and 2016 were included in this study. Twenty clinical and twenty histological variables were tested for their association with a composite end-point of doubling of serum creatinine, ESRD and death. Univariate and multivariate Cox proportional hazard regression analysis were performed to identify independent predictors of outcome. Results: During a median follow-up period of 48 months (IQR: 17.5–120 months), 21.6% of patients reached the composite end-point. The overall survival rate of our cohort was 89% at one year, 86% at five years, 74% at 10 years and 64% at 20 years. Patients with Class IV LN showed the worst prognosis with 44% survival at 10 years, while those who additionally showed crescents and global sclerosis on kidney biopsy had an even lower survival of 21% and 0% at 10 years, respectively. After multivariate adjustment, we identified estimated glomerular filtration rate at baseline (HR, 0.91 per ml/min /1.73 m²; 95% CI, 0.84 to 0.99), 24-hour proteinuria at baseline (HR, 2.04 per g/d; 95% CI, 1.19 to 3.5), crescents (HR, 1.068 per %; 95% CI, 1.003 to 1.091), global sclerosis (HR, 1.036 per %; 95% CI, 0.984 to 1.091), presence of adhesions (HR, 9.2; 95% CI, 1.38 to 61.2) and tubulitis (HR, 13.1; 95% CI; 1.3 to 131) as independent predictors of outcome in our cohort of LN. Conclusions: Our study identified glomerular (crescents, global sclerosis, adhesions) and tubulointerstitial (tubulitis) lesions, in addition to clinical variables (renal function, 24-hour proteinuria), as important predictors of renal outcome, independent of the ISN/RPS classification. We suggest that the ISN/RPS classification could be improved by a quantitative assessment of glomeruli with active and chronic lesions and by a greater emphasis given to tubulointerstitial lesions.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disorders caused by a loss of tolerance to endogenous nuclear antigens triggering an aberrant autoimmune response targeting various tissues. Lupus nephritis (LN), a major cause of morbidity and mortality in patients with SLE, affects up to 60% of patients. The recent insights into the genetic and molecular basis of SLE and LN paved the way for newer therapies to be developed for these patients. Apart from the traditional B-cell-centered view of this disease pathogenesis, acknowledging that multiple extrarenal and intrarenal pathways contribute to kidney-specific autoimmunity and injury may help refine the individual therapeutic and prognostic characterization of such patients. Accordingly, the formerly induction-maintenance treatment strategy was recently challenged with the exciting results obtained from the trials that evaluated add-on therapy with voclosporin, belimumab, or Obinutuzumab. The scope of this review is to provide an insight into the current knowledge of LN pathogenesis and future therapeutic strategies.

Since the identification of PLA2R (M-type phospholipase A2 receptor) as the first human antigenic target in primary membranous nephropathy (MN), perpetual progress has been made in understanding the pathogenesis of this disease. Accumulating clinical data support a pathogenic role for the anti-PLA2R antibodies (PLA2R ABs), but confirmation in an animal model is still lacking. However, PLA2R ABs were related to disease activity and outcome, as well as to response therapy. Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. Nevertheless, validation of a universal assay with high precision and definition of cut-off levels, followed by larger studies with a prolonged follow-up period, are needed to confirm these prospects.

Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m²). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.

IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon. We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period. Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m², compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m² in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects. Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.

Acute kidney injury (AKI) is a common complication after allogeneic stem cell transplantation; however, its incidence and outcome in patients transplanted for multiple myeloma (MM) is unknown. We evaluated the incidence, severity, and risk factors for AKI within the first 30 days after autologous stem cell transplantation (ASCT) for MM. We prospectively followed 185 consecutive patients with MM, without chronic renal replacement therapy, who underwent ASCT; 12.5% of patients had MM‐associated amyloidosis. AKI occurred in 19 (10.3%) patients, 8 ± 3 days after ASCT, with 18 patients (9.7%) stage 1 and one patient (0.6%) stage 2 AKI. The development of AKI was not associated with reduced overall survival and recovery of kidney function was evident in 68.4% of patients at 3 months. In Cox regression analysis, preexisting–chronic kidney disease (HR 7.01, CI 95% 2.04‐24.09; P = 0.002), serum beta2 microglobulin (HR 3.05, CI 95% 1.10‐8.44; P = 0.03), and mucositis grade 3/4 (HR 1.29, CI 95% 1.08‐1.53; P = 0.003) were independent risk factors for AKI. Our results suggest that AKI occurs with low incidence and reduced severity after ASCT for MM. Prophylactic measures in patients with preexisting–kidney failure may further reduce this risk.