Significance Statement: A cyclic regimen of corticosteroid and cyclophosphamide is the first-line therapy for membranous nephropathy. Rituximab is superior to conservative treatment and noninferior to cyclosporine in inducing remission; it also may have a more favorable safety profile compared with cyclic therapy, but a head-to-head comparison of rituximab versus cyclic therapy is lacking. Using a multisite design, the authors designed a pilot randomized trial to obtain estimates of the effects of the two therapies and to assess the recruitment potential of a noninferiority trial. They found rituximab and cyclophosphamide may have comparable effects on disease remission and a similar short-term safety profile. These data suggest that, although rituximab may be a valid alternative to cyclic therapy for patients with membranous nephropathy, a head-to-head pragmatic comparison would require a large, global, noninferiority trial. Background: A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking. Methods: We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events. Results: At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen. Conclusions: This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial. Clinical Trial registry name and registration number: Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535

Background: Myroides spp. are common environmental organisms and they can be isolated predominantly in water, soil, food and in sewage treatment plants. In the last two decades, an increasing number of infections such as urinary tract infections and skin and soft tissue infections, caused by these microorganisms has been reported. Selection of appropriate antibiotic therapy to treat the infections caused by Myroides spp. is difficult due to the production of a biofilm and the organism’s intrinsic resistance to many antibiotic classes. Case presentation: We report the case of a 69-year-old immunocompromised patient who presented with repeated episodes of macroscopic haematuria, from Northern Italy. A midstream urine sample cultured a Gram negative rod in significant amounts (> 10⁵ colony-forming units (cfu)/mL), which was identified as Myroides odoratimimus. The patient was successfully treated with trimethoprim/sulfamethoxazole after antibiotic susceptibility testing confirmed its activity. Conclusion: This case underlines the emergence of multidrug resistant Myroides spp. which are ubiquitous in the environment and it demands that clinicians should be more mindful about the role played by atypical pathogens, which may harbour or express multidrug resistant characteristics, in immunocompromised patients or where there is a failure of empiric antimicrobial therapy.

In humans, heterozygous mutations of hepatocyte nuclear factor 1beta (HNF1B) are responsible for a dominant inherited disease with both renal and extrarenal phenotypes. HNF1B nephropathy is the umbrella term that includes the various kidney phenotypes of the disease, ranging from congenital anomalies of the kidney and urinary tract (CAKUT), to tubular transport abnormalities, to chronic tubulointerstitial and cystic renal disease. We describe 7 families containing 13 patients with ascertained HNF1B nephropathy. All patients underwent genetic testing and clinical, laboratory, and instrumental assessment, including renal imaging and evaluation of extrarenal HNF1B manifestations. Significant inter- and intrafamilial variability of HNF1B nephropathy has been observed. In our cohort, HNF1B pathogenic variants presented with renal cysts and diabetes syndrome (RCAD); renal cystic phenotype mimicking autosomal dominant polycystic kidney disease (ADPKD); autosomal dominant tubulointerstitial kidney disease (ADTKD) with or without hyperuricemia and gout; CAKUT; and nephrogenic diabetes insipidus (NDI). Of note, for the first time, we describe the occurrence of medullary sponge kidney (MSK) in a family harboring the HNF1B whole-gene deletion at chromosome 17q12. Genotype characterization led to the identification of an additional 6 novel HNF1B pathogenic variants, 3 frameshift, 2 missense, and 1 nonsense. HNF1B nephropathy may present with a highly variable renal phenotype in adult patients. We expand the HNF1B renal clinical picture to include MSK as a potential new finding. Finally, we expand the allelic repertoire of the disease by adding novel HNF1B pathogenic variants.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare inherited disorder characterized by progressive loss of kidney function, nonsignificant urinalysis and tubulointerstitial fibrosis. ADTKD progresses to end stage renal disease (ESRD) in adulthood. The classification of ADTKD is an evolving concept and the agreement is now that, due to the overlap in terms of phenotype characteristics, this should be based on the involved gene. The umbrella term ADTKD therefore includes different conditions as follows: ADTKD-UMOD, ADKTD-MUC1, ADTKD-REN, and ADTK-HNF1B, with ADTKD-SEC61A1 and ADTKD-DNAJB11 as a further rare and atypical diagnosis recently described.

COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the prognosis and the severity of the disease, and can in turn lead to an increased need of mechanical ventilation, antibiotic therapy and to a higher mortality. Here we describe, for the first time in Europe, a fatal case of co-infection between SARS-CoV-2 and Pneumocystis jirevocii in a kidney transplant recipient.

Background Causative mutations in the GANAB gene have been described in only 14 families, 9 diagnosed with late-onset Autosomal Dominant Polycystic Kidney Disease (ADPKD) and 5 with Autosomal Dominant Polycystic Liver Disease (ADPLD). Case Diagnosis of ADPKD was made in a 45-year old man during screening for hernia repair. CT scan showed enlarged cystic kidneys, nephrolithiasis and normal-sized liver with multiple cysts. Hematuria, hypertension and aortic root dilatation were also documented. Renal function was normal. Molecular analysis of PKD genes disclosed a heterozygous p.R839W GANAB variant inherited from the mother. Both his elderly parents presented normal-sized bilateral cystic kidneys but normal renal function. The GANAB-ADPKD mother had no liver cysts. The father was screened for PKD-related genes and no variant was found. Genetic analysis We describe a new family with late-onset ADPKD due to the p.R839W GANAB variant, previously reported in a severe ADPLD patient, requiring liver transplantation. Discussion Since ADPKD-GANAB is an ultrarare, recently described disease, reporting further patients may help unraveling gene-related phenotype. In our patients the p.R839W GANAB variant was not related to severe ADPLD, as previously reported, but with mild ADPKD and a plethora of renal and extrarenal manifestations, usually described in PKD1/PKD2 patients. The evidence that the GANAB variant may cause both ADPKD and ADPLD of variable severity supports that renal and hepatic cystogenesis are the result of a common defective polycystin-1 pathway. Graphic abstract