The Impact of Infections on the Progression of Chronic Kidney Disease.

Background and Objective: Infectious diseases continue to be a global burden and their impact is even worse if the patients already have other comorbidities. Because chronic kidney disease is very frequent, affecting 10% of the population, our study aims to explore the impact that infectious events have on its progression. Material and Methods: This is a retrospective, observational study based on a cohort of 238 dialyzed patients from the Nephrology Clinic of "Dr. Carol Davila" Clinical Hospital of Nephrology, Bucharest, who were followed from their first visit for five years, between 1 January 2007 and 1 January 2022. For each of them, the presence of an infectious event and the moment of the initiation of dialysis were recorded. Results: Statistical analysis showed that the patients who had at least one infectious episode were older (p = 0.004), their hemoglobin and lymphocytes were significantly lower (p = 0.03 and p = 0.02, respectively) and the time until the initiation of dialysis was lower (p = 0.007). Also, the preservation of kidney function was influenced by the number and the severity of infectious episodes. In the univariate Cox model, the following variables were associated with increased risk of dialysis: advanced age (p: 0.009; HR: 1.021; CI: 1.005 to 1.036), low hemoglobin (p: 0.001; HR: 0.861; CI: 0.786 to 0.943), previous diagnosis of chronic obstructive pulmonary disease (p: 0.002; HR: 2.467; CI: 1.376 to 4.424), presence of hematuria (p: 0.03; HR: 1.604; CI: 1.047 to 2.457) and increased values of proteinuria (p: 0.01; HR: 1.122; CI: 1.028 to 1.224) and of serum creatinine measured both at the time of the first visit and at the time of each infectious event (p: <0.001; HR: 1.262; CI: 1.141 to 1.396). Also, the presence of an infectious episode was associated with a 1.7-fold increase in the risk of dialysis initiation. The independent predictors of survival identified by the multivariate Cox model were age (p: 0.004; HR: 1.034; CI: 1.010-1.058), serum creatinine (p: <0.001; HR: 1.421; CI: 1.203 to 1.658) and proteinuria (p: <0.001; HR: 1.241; CI: 1.126 to 1.369) at the time of enrollment, but also the presence of an infectious episode during the patient's evolution (p: 0.04; HR: 1.705; CI: 1.013 to 2.868). Conclusions: In the evolution of patients with chronic kidney disease, an active search for individual factors favoring the occurrence of infectious episodes should be taken into consideration to prevent a faster progression toward end-stage kidney disease.

Periostin as a Biomarker in the Setting of Glomerular Diseases-A Review of the Current Literature.

Chronic kidney disease (CKD) is a highly prevalent and potential progressive condition with life-threatening consequences. Glomerular diseases (glomerulopathies) are causes of CKD that are potentially amenable by specific therapies. Significant resources have been invested in the identification of novel biomarkers of CKD progression and new targets for treatment. By using experimental models of kidney diseases, periostin has been identified amongst the most represented matricellular proteins that are commonly involved in the inflammation and fibrosis that characterize progressive kidney diseases. Periostin is highly expressed during organogenesis, with scarce expression in mature healthy tissues, but it is upregulated in multiple disease settings characterized by tissue injury and remodeling. Periostin was the most highly expressed matriceal protein in both animal models and in patients with glomerulopathies. Given that periostin is readily secreted from injury sites, and the variations in its humoral levels compared to the normal state were easily detectable, its potential role as a biomarker is suggested. Moreover, periostin expression was correlated with the degree of histological damage and with kidney function decline in patients with CKD secondary to both inflammatory (IgA nephropathy) and non-inflammatory (membranous nephropathy) glomerulopathies, while also displaying variability secondary to treatment response. The scope of this review is to summarize the existing evidence that supports the role of periostin as a novel biomarker in glomerulopathies.

Anti-phospholipase A2 receptor antibody screening in nephrotic syndrome may identify a distinct subset of patients with primary membranous nephropathy.

PURPOSE: We sought to investigate the utility of anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary MN in patients with nephrotic syndrome (NS). METHODS: All consecutive patients with NS admitted in our department, between 01.01.2015 and 31.12.2019 were screened for anti-PLA2R antibodies by an ELISA assay (EUROIMMUN, Lübeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml. Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis. RESULTS: Of the 203 patients with NS, we identified 67 patients with "high" titer of anti-PLA2R antibodies (> 20 RU/ml) and 47 patients with "intermediate" titer (2-20 RU/ml). In the entire cohort, the area under the curve (AUC) was 0.83 (95% CI 0.78-0.89; p < 0.001). With a cutoff of 20 RU/ml, the anti-PLA2R antibodies had a 64% sensitivity (95% CI 53-73%) and 94% specificity (95% CI 88-97%) to discriminate MN from other causes of NS. In addition, the PPV and NPV were 91% (95% CI 82-95%) and 75% (95% CI 69-79%). When analyzing the posttest effect, we identified a LR+ of 11.56 (95% CI 5.2-25.2) and LR- of 0.38 (95% CI 0.29-0.5). The overall accuracy of the test was 80.3% (95% CI 74-85%) and the diagnostic odds ratio was 30.42. When performing subgroup analysis, we identified that in younger patients, in those with preserved renal function or with negative workup for secondary causes, the diagnostic performance of anti-PLA2R antibodies was improved, the sensitivity increasing to 68-71%, the PPV to 93-95% and the LR+ to 12.23-15.4. CONCLUSION: Serum anti-PLA2R antibody screening in patients with NS is a useful method for the diagnosis of primary MN. In younger patients (less than 60 years old) who have a preserved renal function and a negative workup for secondary causes of NS, a positive anti-PLA2R test highly predicts a diagnosis of primary MN.

Chronic Kidney Disease, Urinary Tract Infections and Antibiotic Nephrotoxicity: Are There Any Relationships?

Chronic kidney disease (CKD) has been a constant burden worldwide, with a prevalence of more than 10% of the population and with mortality reaching 1.2 million deaths and 35.8 million disability-adjusted life years (DALYs) in 2017, as it is claimed by the Global Burden of Diseases. Moreover, an increase in its prevalence is expected in the next years due to a rise in the number of people suffering from obesity, diabetes mellitus and hypertension. On the other hand, with cardiovascular morbidity and mortality showing a downward trend, maybe it is time to focus on CKD, to minimize the preventable risk factors involved in its progression toward end-stage kidney disease (ESKD) and to offer a better quality of life. Another major health burden is represented by infectious diseases, particularly urinary tract infections (UTIs), as it is considered that approximately 40-50% of women and 5% of men will have at least one episode during their lifetime. Additionally, CKD consists of a constellation of immunological and metabolical disturbances that lead to a greater risk of UTIs: increased apoptosis of lymphocytes, elevated levels of tumor necrosis factor α and interleukin 6, which lower the function of neutrophils and increased levels of uremic toxins like p-cresyl sulfate and indoxyl sulfate, which alter the adherence and migration of leukocytes to the sites of injury. Moreover, UTIs can lead to a more rapid decline of kidney function, especially in stages G3-G5 of CKD, with all the complications involved. Last, but not least, antibiotherapy is often complicated in this category of patients, as antibiotics can also negatively affect the kidneys. This review will try to focus on the particularities of the urinary microbiome, asymptomatic bacteriuria and UTIs and the subtle balance between the risks of them and the risks of antibiotherapy in the evolution of CKD.