The specific B-cell depleting anti-CD20 monoclonal antibody rituximab (RTX) is effective in terms of the treatment of various immune-mediated glomerulopathies. The administration of RTX has been shown to be reliable and highly effective particularly in patients with ANCA-associated vasculitis, which is manifested predominantly with non-nephrotic proteinuria. Stable long-term B-cell depletion is usually readily attained in such patients using standard dosing regimens. However, in patients with nephrotic syndrome and non-selective proteinuria, the RTX pharmacokinetics is altered profoundly and RTX does not maintain high enough levels for a sufficiently long period, which may render RTX treatment ineffective. Since complement-derived cytotoxicity is one of the important modes of action of RTX, hypocomplementemia, frequently associated with systemic lupus erythematodes, may act to hamper the efficacy of RTX in the treatment of patients with lupus nephritis. This review provides a description of RTX pharmacokinetics and pharmacodynamics in several selected glomerulopathies, as well as the impact of proteinuria, anti-drug antibodies and other clinical variables on the clearance and volume of distribution of RTX. The impact of plasmapheresis and peritoneal dialysis on the clearance of RTX is also discussed in the paper. A review is provided of the potential association between pharmacokinetic and pharmacodynamic alterations in various kidney-affecting glomerular diseases, the sustainability of B-cell depletion and the clinical efficacy of RTX, with proposals for potential dosing implications. The role of therapeutic drug monitoring in treatment tailoring is also discussed, and various previously tested RTX dosing schedules are compared in terms of their clinical and laboratory treatment responses. Since alternative anti-CD20 molecules may prove effective in RTX unresponsive patients, their pharmacokinetics, pharmacodynamics and current role in the treatment of glomerulopathies are also mentioned.

Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients' characteristics, rituximab levels and anti-rituximab antibodies. The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.

Our study presents a novel collagen wound dressing prepared from freshwater fish skin (Cyprinus Carpio) collagen type I. Half of the sponges were cross-linked with carbodiimide. The cross-linked and non-cross-linked collagen sponges were subsequently impregnated with gentamicin and lyophilized thus allowing for the attainment of the appropriate gentamicin content without the removal thereof during the cross-linking stage. The structure was evaluated via micro-CT and infrared spectrometry and the structural stability and gentamicin release properties were evaluated in phosphate buffer solution. The sponges were further tested via a rat model of an infected wound with Pseudomonas aeruginosa inoculation and compared with a reference commercial product. The sponges thus prepared provided a degree of open porosity that was comparable to or higher than that of the reference commercial product. Spectrometry analysis revealed that the cross-linked collagen sponge and reference commercial product sponge preserved their secondary collagen structure after 168 h while early accelerated degradation was observed with respect to the non-cross-linked collagen sponge. Gentamicin was released rapidly from all the sponges. Compared to those animals with gentamicin-containing sponges or gentamicin administered intramuscularly, the animals with the cross-linked collagen sponge without gentamicin exhibited marked clinical and laboratory infection signs. Both the administration routes (intramuscular and via gentamicin-containing sponges) provided similar gentamicin plasma levels. The resulting highly homogeneous product which was characterized by excellent structural and clinical properties proved effective in terms of the treatment of a surgical wound infection in a rat model. We demonstrated that all the gentamicin was released from the sponge and was absorbed in the systemic circulation. This is the first time that Cyprinus Carpio collagen has been used in the preparation of wound dressings. Thus, gentamicin-containing sponges provide a promising tool for the treatment and prevention of surgical site infections.