Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the functional defect of alanine-glyoxylate aminotransferase that results in the overproduction of oxalate. It can be devastating especially for kidneys, leading to end-stage renal disease (ESRD) during the first 2 to 3 decades of life in most patients. Consequently, many PH1 patients need kidney transplantation. However, because PH1 is caused by a liver enzyme deficiency, the only cure of the metabolic defect is liver transplantation. Thus, current transplant strategies to treat PH1 patients with ESRD include dual liver–kidney transplantation. However, the morbidity and mortality associated with liver transplantation make these strategies far from optimal. Fortunately, a therapeutic revolution is looming. Indeed, innovative drugs are being currently tested in clinical trials, and preliminary data show impressive efficacy to reduce the hepatic overproduction of oxalate. Hopefully, with these therapies, liver transplantation will no longer be necessary. However, some patients with progressing renal disease or those who will be diagnosed with PH1 at an advanced stage of chronic kidney disease will ultimately need kidney transplantation. Here we review the current knowledge on this subject and discuss the future of kidney transplant management in PH1 patients in the era of novel therapies.

The efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs). In this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied. A total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads. NR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.

Kidney transplant recipients (KTRs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have an increased risk of mortality compared with the general population and hemodialysis patients. As these patients are immunosuppressed, it might seem obvious to attribute this excess mortality to the impaired immunity induced by immunosuppression. In line with this reasoning is the low immune response, both cellular and humoral, that KTRs mount in response to the anti–SARS-CoV-2 vaccine; however, acute respiratory distress syndrome associated with coronavirus disease 2019 is triggered by a state of inflammation and cytokine release syndrome that lead to pulmonary damage and increased mortality. In that context, immunosuppressive treatment dampening the immune response could, in theory, be potentially beneficial. This review aims at analyzing the current knowledge on the impact of immunosuppressive treatment on mortality in SARS-CoV-2–infected KTRs, the optimal management of immunosuppression in the coronavirus disease 2019 era, and the vaccine response and management in immunosuppressed KTRs.

Background: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. Methods: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m² at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. Results: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11–58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57–76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m² in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m². Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. Conclusions: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

The use of high-risk renal grafts for transplantation requires the optimization of pretransplant assessment and preservation reconditioning strategies to decrease the organ discard rate and to improve short- and long-term clinical outcomes. Active oxygenation is increasingly recognized to play a central role in dynamic preservation strategies, independent of preservation temperature, to recondition mitochondria and to restore the cellular energy profile. The oxygen-related decrease in mitochondrial succinate accumulation ameliorates the harmful effects of ischemia-reperfusion injury. The differences between normothermic and hypothermic machine perfusion with regard to organ assessment, preservation, and reconditioning, as well as the logistic and economic implications, are factors to take into consideration for implementation at a local level. Therefore, these different techniques should be considered complementary to the perfusion strategy selected depending on functional intention and resource availability. This review provides an overview of the current clinical evidence of normothermic and oxygenated hypothermic machine perfusion, either as a continuous or end-ischemic preservation strategy, and future perspectives.