Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.

The implementation of whole‐exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single‐platform, high‐resolution liquid chromatography quadrupole time of flight (LC‐QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM‐suspected patients. This method, which we termed “next‐generation metabolic screening” (NGMS), can detect >10,000 features in each sample. In the NGMS workflow, features identified in patient and control samples are aligned using the “various forms of chromatography mass spectrometry (XCMS)” software package. Subsequently, all features are annotated using the Human Metabolome Database, and statistical testing is performed to identify significantly perturbed metabolite concentrations in a patient sample compared with controls. We propose three main modalities to analyze complex, untargeted metabolomics data. First, a targeted evaluation can be done based on identified genetic variants of uncertain significance in metabolic pathways. Second, we developed a panel of IEM‐related metabolites to filter untargeted metabolomics data. Based on this IEM‐panel approach, we provided the correct diagnosis for 42 of 46 IEMs. As a last modality, metabolomics data can be analyzed in an untargeted setting, which we term “open the metabolome” analysis. This approach identifies potential novel biomarkers in known IEMs and leads to identification of biomarkers for as yet unknown IEMs. We are convinced that NGMS is the way forward in laboratory diagnostics of IEMs.

Background. Many papers are published on cohorts with unilateral multicystic dysplastic kidney (MCDK) patients, but show variable results as to the incidence of associated urinary tract abnormalities. The objective of this study was to describe the status of the urinary tract, including contralateral hypertrophy and malformations, in patients with unilateral MCDK based on a meta-analysis of the literature, taking into account the timing of diagnosis (pre- versus postnatal) as a possible source of bias. Methods. A systematic review of the scientific literature in English was conducted using PubMed and Embase. A meta-analysis was performed with the studies that were identified using our reproducible search. Results. Based on analysis of the data in 19 populations, the overall incidence of unilateral MCDK is 1 in 4300 with an increasing trend over the years. A total of 67 cohorts with over 3500 patients with unilateral MCDK were included in the meta-analysis. Fifty-nine percent of patients were male and the MCDKs were significantly more often found on the left side (53.1%). Associated anomalies in the solitary functioning kidney were found in 1 in 3 patients, mainly vesicoureteric reflux (VUR, in 19.7%). In patients with VUR, 40% have severe contralateral VUR, defined as grade III–V. Contralateral hypertrophy, present in 77% of patients after a follow-up of at least 10 years, showed a trend to be less pronounced in patients with VUR. Timing of the diagnosis of MCDK did not essentially influence the results. Conclusions. These aggregate results provide insight into the incidence, demographic data and associated anomalies in patients with unilateral MCDK. One in three patients with unilateral MCDK show anomalies in the contralateral, solitary functioning kidney. However, studies into the long-term consequences of these anomalies are scarce.

Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progression to CKD. However, challenges remain in distinguishing patients with a high risk for disease progression from those patients without a high risk of disease progression. Although it is hypothesized that glomerular hyperfiltration in the lowered number of nephrons underlies the impaired renal prognosis in the solitary functioning kidney, the high proportion of ipsilateral congenital anomalies of the kidney and urinary tract in these patients may further influence clinical outcome. Pathogenic genetic and environmental factors in renal development have increasingly been identified and may play a crucial role in establishing a correct diagnosis and prognosis for these patients. With fetal ultrasound now enabling prenatal identification of individuals with a solitary functioning kidney, an early evaluation of risk factors for renal injury would allow for differentiation between patients with and without an increased risk for CKD. This review describes the underlying causes and consequences of the solitary functioning kidney from childhood together with its clinical implications. Finally, guidelines for follow-up of solitary functioning kidney patients are recommended.