Immune abnormalities in IgA nephropathy.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and it is characterized by mesangial IgA deposition. Asymptomatic hematuria with various degrees of proteinuria is the most common clinical presentation and up to 20%-40% of patients develop end-stage kidney disease within 20 years after disease onset. The pathogenesis of IgAN involves four sequential processes known as the "four-hit hypothesis" which starts with the production of a galactose-deficient IgA1 (gd-IgA1), followed by the formation of anti-gd-IgA1 IgG or IgA1 autoantibodies and immune complexes that ultimately deposit in the glomerular mesangium, leading to inflammation and injury. Although several key questions about the production of gd-IgA1 and the formation of anti-gd-IgA1 antibodies remain unanswered, a growing body of evidence is shedding light on the innate and adaptive immune mechanisms involved in this complex pathogenic process. Herein, we will focus on these mechanisms that, along with genetic and environmental factors, are thought to play a key role in disease pathogenesis.

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.

Use of peritoneal dialysis for acute kidney injury during the COVID-19 pandemic in New York City: a multicenter observational study.

To demonstrate feasibility of acute peritoneal dialysis (PD) for acute kidney injury during the coronavirus disease 2019 (COVID-19) pandemic, we performed a multicenter, retrospective, observational study of 94 patients who received acute PD in New York City in the spring of 2020. Patient comorbidities, severity of disease, laboratory values, kidney replacement therapy, and patient outcomes were recorded. The mean age was 61 ± 11 years; 34% were women; 94% had confirmed COVID-19; 32% required mechanical ventilation on admission. Compared to the levels prior to initiation of kidney replacement therapy, the mean serum potassium level decreased from 5.1 ± 0.9 to 4.5 ± 0.7 mEq/L on PD day 3 and 4.2 ± 0.6 mEq/L on day 7 (P < 0.001 for both); mean serum bicarbonate increased from 20 ± 4 to 21 ± 4 mEq/L on PD day 3 (P = 0.002) and 24 ± 4 mEq/L on day 7 (P < 0.001). After a median follow-up of 30 days, 46% of patients died and 22% had renal recovery. Male sex and mechanical ventilation on admission were significant predictors of mortality. The rapid implementation of an acute PD program was feasible despite resource constraints and can be lifesaving during crises such as the COVID-19 pandemic.

COVID-19 and the Kidney: A Worrisome Scenario of Acute and Chronic Consequences.

Acute kidney injury (AKI) is a common finding in patients with coronavirus disease 2019 (COVID-19) and has been associated with higher rates of death when compared to COVID-19 patients without kidney injury. Whereas the definitive pathogenesis of COVID-19-related AKI (CoV-AKI) is not clear, histopathologic evidence seems to point at multiple etiologies for the disease, including indirect and direct viral kidney injury. The high incidence of CoV-AKI, along with the aggressive clinical presentation of this entity, have increased the demands for kidney replacement therapies, rapidly overwhelming the supplies of healthcare systems even in major tertiary care centers. As a result, nephrologists have come up with alternatives to maximize the efficiency of treatments and have developed non-conventional therapeutic alternatives such as the implementation of acute peritoneal dialysis for critically ill patients. The long-term implications of CoV-AKI are yet unknown, though early studies suggest that around one third of the patients who survive will remain dependent on kidney replacement therapy. Nephrologists and healthcare workers need to be familiar with the clinical presentation and therapeutic challenges of CoV-AKI in order to develop strategies to mitigate the burden of the disease for patients, and for services providing kidney replacement therapies.

Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching Sessions.

Background: Although urine microscopy is an important step in the initial evaluation of a patient with kidney disease, internal medicine residents have minimal exposure to this technique during their training. The goal of this study was to understand knowledge of and attitudes toward urine microscopy among internal medicine residents and to implement virtual urine microscopy teaching sessions. Methods: A voluntary, anonymous, online survey was sent to all of the categorical internal medicine residents (n=131) training at the Icahn School of Medicine at Mount Sinai (ISMMS). The survey included 13 questions to assess attitudes toward, experience with, and clinical interpretation of urine microscopy specimens. In response to the survey results, we implemented virtual urine microscopy teaching sessions using video conferencing software that incorporated real-time urine sediment analysis with nephrology fellows and attending nephrologists. Results: The survey response rate was 45% (59 of 131). Forty-seven percent (28 of 59) of respondents reported performing urine microscopy at least once during their training, and 75% (44 of 59) of respondents did not feel comfortable performing urine microscopy. The majority of residents (92%; 54 of 59) reported they felt urine microscopy was very helpful or somewhat helpful in the evaluation of patients with AKI. Overall, 41% of responses to clinical interpretation questions were considered correct. Following survey completion, virtual urine microscopy sessions were held monthly and well received by the participants. Conclusions: Our study found that internal medicine residents perceive urine microscopy as a helpful diagnostic tool, although lack the skills to perform and interpret urine microscopy sediments. Virtual educational sessions using video conferencing software are a technically feasible approach to teaching urine microscopy to internal medicine residents. Future studies include a study of the effect of these sessions on learning of urine microscopy. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2021_01_28_KID0006282020.mp3.