Nephron最新文献

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.

Alport syndrome (AS) is a hereditary kidney disorder of type IV collagen caused by pathogenic variants in the COL4A3, COL4A4 and COL4A5 genes. Previously several cases of digenic AS, caused by two pathogenic variants in two of the three COL4A genes, have been reported. Patients with digenic AS may present with a more severe phenotype compared to patients with single variants, depending on the percentage affected type IV trimeric collagen chain. We report a newly discovered case of trigenic AS. A 52-year-old female presented with hematuria at the age of 24 years and developed hypertension by the age of 30. Over the years she developed chronic kidney disease; the most recent eGFR was 44ml/min/1.73m2. She has symmetric high-tone sensorineural hearing loss. Full genetic analysis revealed a heterozygous pathogenic variant c.2691del in COL4A3, a heterozygous pathogenic variant c.1663dup in COL4A4, and a complete heterozygous deletion of COL4A5. We describe the first patient with AS caused by pathogenic variants in all three COL4A genes, designated trigenic AS. This case report emphasizes the importance of examining all three COL4A genes, even in patients with a mild Alport phenotype, for optimal follow-up of the patient and adequate genetic counseling of family members.

Introduction: In pediatric kidney patients, where clinical presentation is often not fully developed, and renal biopsy is too risky or inconclusive, it may be difficult to establish the underlying pathology. In cases such as these, genetic diagnosis may be used to guide treatment, prognosis, and counseling. Given the large number of genes involved in kidney disease, introducing next-generation sequencing with extended gene panels as part of the diagnostic algorithm presents a viable solution.

Methods: A cohort of 87 consecutive independent cases (83 children and 4 terminated pregnancies) with renal disease was recruited. Exome sequencing with MiSeq or NovaSeq 6000 (Illumina) platforms and analysis of extended gene panels were used for genetic testing.

Results: Depending on the presenting pathology, the cases were grouped as patients with glomerular disease, ciliopathies, congenital anomalies, renal electrolyte imbalances, and chronic/acute kidney disease. The overall diagnostic yield was approximately 42% (37 out of 87), with most disease-causing mutations found in COL4A3, COL4A4, COL4A5, and PKHD1 genes. A change or clarification of preliminary diagnosis or adjustment of initial treatment plan based on the results of the genetic testing was made for approximately one-third of the children with meaningful genetic findings (11 out of 37).

Discussion: Our results prove the value of targeted exome sequencing as a non-invasive, versatile, and reliable diagnostic tool for pediatric renal disease patients. Providing genetic diagnosis will help for a better understanding of disease etiology and will give the basis for optimal clinical management and insightful genetic counseling.

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) have beneficial effects on the renal function of chronic kidney disease (CKD) patients, although the types of patients suitable for this treatment remain unclear.

Methods: A retrospective observational study was conducted on CKD patients who were treated with SGLT2I in our department from 2020 to 2023. The estimated glomerular filtration rate (eGFR) just before treatment was defined as the baseline and the difference between pre-and post-treatment eGFR slopes were used to compare the improvement of renal function. Logistic regression analysis was used to evaluate the independent factors for its improvement.

Results: A total of 128 patients were analyzed (mean age: 67.2 years; number of women: 28 [22%]). The mean eGFR was 42.1 mL/min/1.73 m2, and urine protein was 0.66 g/gCr. The eGFR slopes of patients with an eGFR <30 mL/min/1.73 m2 were improved significantly after treatment (-0.28 to -0.14 mL/min/1.73 m2/month, p < 0.001) but were worsened in patients with an eGFR ≥30 mL/min/1.73 m2. Logistic analysis for the improvement in eGFR slopes showed that women (odds ratio [OR], 5.63; 95% confidence interval [CI], 1.16-27.3; p = 0.03), use of mineralocorticoid receptor antagonists (OR, 11.79; 95% CI, 1.05-132.67; p = 0.012) and rapid decline of eGFR before treatment (OR, 12.8 per mL/min/1.73 m2/month decrease in eGFR; 95% CI, 3.32-49.40; p < 0.001) were significant independent variables.

Conclusion: SGLT2Is may have beneficial effects, especially for rapid decliners of eGFR, including advanced CKD.

Introduction: The association between magnesium level and progression to acute kidney disease (AKD) in acute kidney injury (AKI) patients was not well studied. With AKI transition to AKD, the burden of the disease on mortality, morbidity, and healthcare costs increases. Serum magnesium disturbances are linked with a decline in renal function and increased risk of death in CKD and hemodialysis patients. This study aims to assess the significance of magnesium derangements as a risk factor for the progression of AKI to AKD in critically ill patients.

Methods: This study was conducted among patients with AKI admitted to the intensive care units at Mayo Clinic from 2007 to 2017. Serum magnesium at AKI onset was categorized into five groups of <1.7, 1.7-1.9, 1.9-2.1, 2.1-2.3, and ≥2.3 mg/dL, with 1.9-2.1 mg/dL as the reference group. AKD was defined as AKI that persisted >7 days following the AKI onset. Logistic regression was used to evaluate the association between magnesium and AKD.

Results: Among 20,198 critically ill patients with AKI, the mean age was 66 ± 16 years, and 57% were male. The mean serum magnesium at AKI onset was 1.9 ± 0.4 mg/dL. The overall incidence of AKD was 31.4%. The association between serum magnesium and AKD followed a U-shaped pattern. In multivariable analysis, serum magnesium levels were associated with increased risk of AKD with the odds ratio of 1.17 (95% CI: 1.07-1.29), 1.13 (95% CI: 1.01-1.26), and 1.65 (95% CI: 1.48-1.84) when magnesium levels were <1.7, 2.1-2.3, and ≥2.3 mg/dL, respectively.

Conclusion: Among patients with AKI, magnesium level derangement was an independent risk for AKD in critically ill AKI patients. Monitoring serum magnesium and proper correction in critically ill patients with AKI should be considered an AKD preventive intervention in future trials.

Background: Lowering dietary salt intake reduces albuminuria, an early marker of renal damage and a sensitive predictor of adverse cardiovascular outcomes. The mechanisms underlying this effect are uncertain but small changes in serum sodium concentration may be important: this retrospective cohort study investigated the hypothesis that higher serum sodium concentration is a risk factor for albuminuria (defined as a urine albumin:creatinine ratio [UACR], ≥3 mg/mmol).

Methods: Primary care data from the Royal College of General Practitioners Research and Surveillance Centre were used to identify 47,294 individuals with a UACR result available between April 2010 and March 2015, and no known albuminuria prior to this. Exclusion criteria were missing or abnormal serum sodium concentration at baseline (<135 or >146 mmol/L); age <18 years; diabetes mellitus; decompensated liver disease; heart failure; and stage 5 chronic kidney disease.

Results: After adjustment for known risk factors, there was a significant "U-shaped" relationship between serum sodium concentration and albuminuria. The lowest risk was associated with a serum sodium of 138-140 mmol/L. In comparison, the risk of albuminuria was 18% higher with a serum sodium of 135-137 mmol/L and 19% higher with a serum sodium of 144-146 mmol/L. There was no association between serum sodium concentration and blood pressure.

Conclusion: The finding of a positive association between higher serum sodium concentration and albuminuria is in support of the hypothesis, but the inverse relationship between serum sodium concentration and albuminuria at lower concentrations warrants further explanation.

Background: Chronic kidney disease (CKD) is a serious public health issue worldwide, but the disease burden of CKD caused by different etiologies and changing trends has not been fully examined.

Methods: We collected data from Global Burden of Disease Study 2019 (GBD 2019), including incident cases, age-standardized incidence rate (ASIR), disability-adjusted life years (DALYs), and age-standardized DALY rate between 1990 and 2019 by region, etiology, age, and sex, and calculated the estimated annual percentage change (EAPC) of the rate to evaluate the epidemiological trends.

Results: Globally, incident cases of CKD increased from 7.80 million in 1990 to 18.99 million in 2019, and DALYs increased from 21.50 million to 41.54 million. ASIR increased with an EAPC of 0.69 (95% uncertainty interval [UI] 0.49-0.89) and reached 233.65 per 100,000 in 2019, while the age-standardized DALY rate increased with an EAPC of 0.30 (95% UI 0.17-0.43) and reached 514.86 per 100,000. North Africa and the Middle East, central Latin America, and North America had the highest ASIR in 2019. Central Latin America had the highest age-standardized DALY rate, meanwhile. Almost all countries experienced an increase in ASIR, and over 50% of countries had an increasing trend in age-standardized DALY rate from 1990 to 2019. CKD due to diabetes mellitus type 2 and hypertension accounted for the largest disease burden with 85% incident cases and 66% DALYs in 2019 of known causes, with the highest growth in age-standardized DALY rate and a similar geographic pattern to that of total CKD. Besides, the highest incidence rate of total and four specific CKDs were identified in people aged 70 plus years, who also had the highest DALY rate with a stable trend after 2010. Females had a higher ASIR, while males had a higher age-standardized DALY rate, the gap of which was most distinctive in CKD due to hypertension.

Conclusion: The disease burden of CKD remains substantial and continues to grow globally. From 1990 to 2019, global incident cases of CKD have more than doubled and DALYs have almost doubled, and surpassed 40 million years. CKD due to diabetes mellitus type 2 and hypertension contributed nearly 2/3 of DALYs in 2019 of known causes, and had witnessed the highest growth in age-standardized DALY rate. Etiology-specific prevention strategies should be placed as a high priority on the goal of precise control of CKD.

The new European Kidney Function Consortium (EKFC) creatinine-based equation has been developed to be applicable over the entire age range (from 2 to 100 years) without any loss of performance in young adults and without loss of continuity in estimating glomerular filtration rate (GFR) between adolescents and adults. This goal is obtained by better taking into account the relationship between serum creatinine (SCr) and age in the estimating GFR model. This is accomplished by rescaling SCr, namely, dividing SCr by so-called Q value which is the median normal value of SCr concentration in a given healthy population. The better performance of the EKFC equation, compared to the current equations, has been shown in large European and African cohorts. Such good results are also suggested in cohorts from China, including in the current issue of Nephron. The good performance of the EKFC equation is observed, especially when the authors used a specific Q value for their populations notwithstanding GFR was measured by a controversial method. Using a population-specific Q value could make the EFKC equation universally applicable.