Nephron最新文献

Introduction: Membranoproliferative glomerulonephritis is currently divided into immunoglobulin-mediated glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G); however, the patients often overlap with histology, complement, clinical and prognostic factors. Our aim was to investigate if an unsupervised clustering method finds different patient groups in 44 IC-MPGN/C3G patients using only histological and clinical data available in everyday clinical work.

Methods: Primary IC-MPGN/C3G adult patients were included whose diagnostic (baseline) native biopsy was obtained in 2006-2017. The biopsies were reassessed and the clinical data at baseline and during follow-up were obtained from the medical records. There were 39 baseline histological and clinical variables included in the unsupervised clustering. Follow-up information was combined with the clustering results.

Results: The clustering resulted in two clusters (n = 24 and n = 20 patients for clusters 1-2, respectively), where cluster 1 had a significantly higher baseline plasma creatinine (mean 213 vs. 104, respectively, p value <0.001) and a lower baseline eGFR than cluster 2 (mean 37 vs. 70, respectively, p value <0.001). Regarding histology, chronic changes such as lobulated glomeruli, mesangial matrix expansion, and glomeruli double contours were more prevalent in cluster 1 (p value <0.001). Biopsy morphology was more often crescentic and membranoproliferative in cluster 1 (p value <0.001). Although the differences were insignificant, cluster 1 patients were in dialysis in the last follow-up or had a progressive disease more often than cluster 2 patients (21% vs. 5%, 38% vs. 10%).

Conclusions: Our results indicate that these patients share greater similarity than the current classification IC-MPGN versus C3G indicates.

Introduction: The first version of Animal Research: Reporting of in vivo Experiments (ARRIVE 1.0) guidelines was introduced to improve reporting of animal research but did not lead to major improvements in this respect. This applied also to animal studies on peritoneal dialysis (PD). Here, we examined the performance of the revised version of these guidelines (ARRIVE 2.0).

Methods: Eighty-nine relevant articles published in 2018-2020 (ARRIVE 1.0 period) and 97 published in 2021-2023 (ARRIVE 2.0 period) were identified in PubMed® and analyzed for completeness and transparency of reporting.

Results: In both periods, most studies were carried out in Asia, on rodents, and concerned the peritoneal pathophysiology. During ARRIVE 2.0, more studies were published in higher impact factor journals with the focus on pharmacology and immunology. Compared to ARRIVE 1.0, general aspects of study design and reporting improved during ARRIVE 2.0 period in studies generated in Europe and USA but did not change significantly in Asia. Detailed analysis showed no global improvement in completeness of reporting key information included in the ARRIVE 2.0 Essential 10 checklist. Articles from both periods were deficient in sample size calculations, use of blinding, recording adverse events and drop-outs, and specification of appropriate statistical methods. The level of reporting during ARRIVE 2.0 did not correspond to the journal impact factor and the presence of recommendations for the use of ARRIVE 2.0 in their instructions to authors.

Conclusion: So far, ARRIVE 2.0 has not produced significant improvements in the reporting of animal studies in PD.

Introduction: Chronic kidney disease (CKD) is associated with an increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF.

Methods: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168,233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124,936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation.

Results: At AF diagnosis eGFR <60 mL/min/1.73 m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded more comorbidities and medications. During 2010-2018 in patients with eGFR <60 mL/min/1.73 m2 prevalence of hypertension, dyslipidaemia, and diabetes increased from 82 to 88%, from 50 to 66% and from 25 to 33%, respectively (<0.001). Throughout the observation period, lipid-lowering medication was underused.

Conclusion: More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR <60 mL/min/1.73 m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but the use of survival-affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.

Background: Urea is the major end-product of protein metabolism in mammals. In carnivores and omnivores, a large load of urea is excreted daily in urine, with a concentration that is 30-100 times above that in plasma. This is important for the sake of water economy. Too little attention has been given to the existence of energy-dependent urea transport that plays an important role in this concentrating activity.

Summary: This review first presents functional evidence for an energy-dependent urea secretion that occurs exclusively in the straight part of the proximal tubule (PST). Second, it proposes a candidate transmembrane transporter responsible for this urea secretion in the PST. SLC6A18 is expressed exclusively in the PST and has been identified as a glycine transporter, based on findings in SLC6A18 knockout mice. We propose that it is actually a glycine/urea antiport, secreting urea into the lumen in exchange for glycine and Na. Glycine is most likely recycled back into the cell via a transporter located in the brush border. Urea secretion in the PST modifies the composition of the tubular fluid in the thick ascending limb and, thus, contributes, indirectly, to influence the "signal" at the macula densa that plays a crucial role in the regulation of the glomerular filtration rate (GFR) by the tubulo-glomerular feedback.

Key messages: Taking into account this secondary active secretion of urea in the mammalian kidney provides a new understanding of the influence of protein intake on GFR, of the regulation of urea excretion, and of the urine-concentrating mechanism.