The latest medical research on Transplant Nephrology

Assess incidence of Acute Kidney Diseas and Disorders (AKD) and Acute Kidney Injury (AKI) episodes and impact on progression of renal dysfunction and risk of all-cause mortality in the community.

Community of 1 863 731 aged > 23 years with at least two serum creatinine measurements. eGFR was calculated using CKD-EPI formula. CKD, AKD and AKI were defined according to the harmonized KDIGO criteria (Lameire 2021). The sCr values and RIFLE scale was used to classify episodes. Progression of renal dysfunction and mortality were evaluated.

56 850 episodes of AKD in 47 972 patients in 4.8 years were identified. AKD incidence of AKD was 3.51 and 12.56/1000 patients/year in non-CKD and CKD, respectively. One AKD episode was observed in 87.3% patients, two in 9.3% and three or more in 3.4%. A second episode was less common in patients without CKD (10.3%) compared to those with CKD (18.4%). Among patients without CKD a total of 43.8% progressed to CKD, and those with previous CKD 63.1% had eGFR decline of > 50%. The risk of progression to CKD was higher in women, older, overweight-obesity and heart failure, as was the risk of eGFR decline > 50% in CKD patients, although the number of AKD episodes was also a risk factor. AKI episodes were observed in 5646 patients with or without CKD. Of these, 12.7% progressed to CKD and of those with pre-existing CKD, 43.2% had an eGFR decline of > 20%. In the toal population mortality within 3 months of detection of AKD episode occurred in 7% patients, and was even higher in patients with AKI, 30.1%.

Acute elevations in serum creatinine in the community may pose a health risk and contribute to the development of CKD. Identification of therapeutic targets and provision of appropriate follow-up for those who survive an episode is warranted.

Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing.

We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors.

In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures (OR 1.68; 95% CI 1.55-1.83). This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 with a PPI prescription for longer than two years (OR 6.85, 95% CI 1.85-25.38). The same was true, when analyzing cumulative PPI doses. Here, patients below the age of 60 with a cumulative PPI dose above 16 000 mg (highest quartile) had the highest risk for fractures (OR 4.62, 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures.

This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.

Chronic kidney disease (CKD) is present in >30% of patients with acute myocardial infarction (MI) and has been associated with lower rates of guideline-directed management and worse prognosis. We investigated the use of guideline-directed management and mortality risk in patients with and without CKD.

A nationwide cohort study based on health care registers encompassing all patients ≥18 years hospitalized with first-time MI in Denmark from 2010-2022 was conducted. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Probability of guideline-directed management and risk of all-cause mortality in patients with and without CKD were calculated from adjusted multivariable logistic and Cox regression models with probabilities and risks standardized to the distribution of confounders in the population.

In total, we identified 21,009 patients who met eligibility criteria. Median age was 72 years, and 61% of patients were males; the median eGFR was 82 ml/min/1.73 m2, and 21% of patients had CKD. The 30-day probabilities of coronary angiography and revascularization were 71% (95% CI 69%-72%) and 78% (95% CI 77-79%), p<0.001; and 52% (95% CI 50%-54%) and 58% (95% CI 58%-59%), p<0.001, in patients with and without CKD, respectively. Probabilities increased during the study period (p for trend 0.05, 0.03, 0.02 and 0.03, respectively). In patients with and without CKD, probability of dual antiplatelet therapy was 67% (95% CI 65%-68%) and 70% (95% CI 69%-71%), p=0.001; while probability of lipid-lowering treatment was 76% (95% CI 75%-78%) and 82% (95% CI 81%-83%), p<0.001. Associated one-year mortality was 21% (95% CI 20%-22%) and 16.4% (95% CI 16%-17%) in patients with and without CKD, respectively. with decreasing mortality rates in both groups during the study period (p for trend 0.03 and 0.01).

Although survival following MI improved for all patients, CKD continued to be associated with lower use of guideline-directed management and higher mortality.

IgA nephropathy (IgAN) is characterised by the production of galactose-deficient IgA1 (GdIgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA-secretion remain unknown.

We carried out flow cytometry analysis of peripheral blood B cells in patients with IgA nephropathy and control subjects with a focus on IgA-expressing B cells to uncover the pathways of B cell activation in IgAN and how these could give rise to pathogenic GdIgA1 antibodies.

In addition to global changes in the B cell landscape - expansion of naive and reduction in memory B cells - IgAN patients present with an increased frequency of IgA-expressing B cells that lack the classical memory marker CD27, but are CD21pos. IgAN patients further have an expanded population of IgApos antibody-secreting cells, which correlate with serum IgA levels. Both IgApos plasmabalsts and CD27neg B cells co-express GdIgA1. Implicating dysregulation at mucosal surfaces as the driver of such B cell differentiation, we found a correlation between lipopolysaccharide (LPS) in the serum and IgAposCD27neg B cell frequency.

We propose that dysregulated immunity in the mucosa may drive de novo B cell activation within germinal centres, giving rise to IgAposCD27neg B cells and subsequently IgA-producing plasmablasts. These data integrate B cells into the paradigm of IgAN pathogenesis and allow to further investigate this pathway to uncover biomarkers and develop therapeutic interventions.