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Introduction: Acute kidney injury (AKI) is a common clinical disease, especially in the intensive care unit. Identification of reliable biomarker is of great clinical significance and benefit the therapy and prevention of AKI. The clinical significance and function of miR-874-3p in AKI development were evaluated in this study aiming to explore a novel biomarker for AKI.

Methods: There were 83 AKI patients and 56 healthy individuals included, and the serum samples were collected. The AKI animal models were established via ischemic/reperfusion (I/R) and LPS on C57BL/6 mice. The expression of miR-874-3p was evaluated using PCR, while the potential downstream targets were also validated in AKI mice. The regulatory mechanism of miR-874-3p was investigated in AKI cell model established with HK-2 cell by I/R.

Results: miR-874-3p was downregulated in both AKI patients and established AKI mice models. The downregulation of miR-874-3p could discriminate against AKI patients and predict poor prognosis of patients. miR-874-3p was negatively correlated with the levels of serum creatine, blood urea nitrogen, CRP, NEU, and PCT and positively correlated with the eGFR of AKI patients. In I/R- and LPS-induced AKI mice, overexpressing miR-874-3p could alleviate renal dysfunction, oxidative stress, and inflammation induced by AKI. Additionally, miR-874-3p could negatively regulate the expression of MSRB3, which was speculated as the potential mechanism underlying the function of miR-874-3p in AKI. Overexpression of miR-874-3p could alleviate the I/R-induced HK-2 cell apoptosis and decreased proliferation, which was reversed by the upregulation of MSRB3.

Conclusion: miR-874-3p served as a diagnostic and prognostic biomarker of AKI and mediate the severity and development of AKI via targeting MSRB3.

Heart disease is one of the leading causes of death in autosomal dominant polycystic kidney disease (ADPKD) patients. Left ventricular hypertrophy (LVH) is an early and severe complication in ADPKD patients. Two decades ago, the prevalence of LVH on echocardiography in hypertensive ADPKD patients was shown to be as high as 46%. Recent studies using cardiac magnetic resonance imaging have shown that the prevalence of LVH in ADPKD patients may be lower. The true prevalence of LVH in ADPKD patients is controversial. There is evidence that factors other than hypertension contribute to LVH in ADPKD patients. Studies have shown that young normotensive ADPKD adults and children have a higher left ventricular mass index compared to controls and that the prevalence of LVH is high in patients with ADPKD whose blood pressure is well controlled. Polycystin-1 (PC-1) and polycystin-2 (PC-2) control intracellular signaling pathways that can influence cardiac function. Perturbations of PC-1 or PC-2 in the heart can lead to profound changes in cardiac structure and function independently of kidney function or blood pressure. PC-1 can influence mammalian target of rapamycin and mitophagy and PC-2 can influence autophagy, processes that play a role in LVH. Polymorphisms in the angiotensin-converting enzyme gene may play a role in LVH in ADPKD. This review will detail the pathophysiology of LVH, beyond hypertension, in ADPKD.

Background: Chronic kidney disease (CKD) affects 11-13% of the world population. The main risk factors for CKD include diabetes, hypertension, and obesity. Metabolic syndrome (MS) is associated with the onset of CKD in the nondiabetic population. Obesity and MS are also risk factors for a worse progression of established CKD. Therapeutic exercise is an effective option to treat and manage obesity, MS, and diabetes in the general population. However, the evidence on the effect of exercise on patients with CKD, obesity, and MS is scarce.

Summary: We evaluated available evidence on the effect of therapeutic exercise in patients with CKD, excluding dialysis, particularly in improving the metabolic risk factors and main renal outcomes: renal function loss and albuminuria/proteinuria. This review includes prospective studies and clinical trials. A total of 44 studies were analysed in 1,700 subjects with renal disease (2-5), including patients with renal transplantation. Most studies did not prove a major effect of exercise on albuminuria/proteinuria, glomerular filtration rate (GFR), obesity, or MS. These results are intriguing and deserve attention. The exploratory nature of most studies, including a low number of cases and short follow-up, might explain the lack of efficacy of exercise in our analysis. Specific aspects like the type of exercise, frequency, intensity, duration, accommodation during follow-up, individualization, safety, and adherence are crucial to the success of therapeutic exercise. The beneficial role of exercise in patients with CKD remains to be determined.

Key messages: Key messages of this review are as follows. (1) The effect of therapeutic exercise on renal and metabolic outcomes in patients with CKD remains to be determined. (2) According to the evidence selected, therapeutic exercise seems to be safe to treat patients with CKD. (3) Most studies are exploratory by nature, with results that need further investigation. (4) Therapeutic exercise is a complex procedure that must be specifically designed to treat patients with CKD.

As nephrology practice is evolving toward precision medicine, and genetic tests are becoming widely available, basic genetic literacy is increasingly required for clinical nephrologists. Yet, decisions based on results of genetic tests are seldom straightforward. We report a 37-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) who was referred for medically assisted reproduction with monogenic preimplantation genetic testing (PGT-M). The PKD1 and PKD2 genes were screened for pathogenic variants. Sequencing analysis revealed the presence of three novel missense single nucleotide variants, two in the PKD1 gene - c.349T>G, p.(Leu117Val) and c.1736C>T, p.(Pro579Leu); and the third in the PKD2 gene - c.1124A>G, p.(Asn375Ser). Bioinformatic predictions of the functional effects of those three missense variants were inconsistent across different software tools. The family segregation analysis, which was mandatory to identify the relevant variant(s) for PGT-M, strongly supported that the disease-causing variant was PKD1 c.349T>G p.(Leu117Val), while the other two were nonpathogenic or, at most, phenotypic modulators. Proving the pathogenicity of novel variants is often complex but is critical to guide genetic counseling and screening, particularly when discussing reproductive alternatives for primary prevention in the progeny of at-risk couples. The family reported herein illustrates those challenges in the setting of ADPKD, and the invaluable importance of a detailed family history and segregation analysis for proper clinical annotation of novel variants. Basic genetic knowledge and proper clinical annotation of novel allelic variants in genes associated with hereditary kidney disorders are increasingly necessary for the contemporary practice of clinical nephrology.

Introduction: Leptospirosis is a globally transmitted zoonotic disease caused by Leptospira spp., a highly mobile, obligate aerobic, spiral-shaped bacteria. Described first by Adolf Weil in 1886, leptospirosis in Germany is rare, leading to a delayed diagnosis due to diverse symptoms. Most cases are mild, but severe forms, like Weil's disease, cause life-threatening complications such as fever, jaundice, hemoptysis, and acute kidney injury (AKI). The aim of this work was to provide a literature review of leptospirosis with renal manifestation based on a case report.

Case presentation: We report the case of an 81-year-old male patient with initially unclear oliguric AKI, bilateral pulmonary infiltrates, and jaundice. After excluding common AKI causes, the expanded patient history suggested possible rat contact in his chicken coop. Finally, we serologically identified an infection with Leptospira spp. by positive IgM, proving that the illness was compatible with classical Weil's disease. The patient underwent temporary hemodialysis and antibiotic treatment with intravenous penicillin G for 2 weeks. Under therapy, the AKI, hyperbilirubinemia, and clinical condition of the patient improved. The patient was discharged after 2 weeks. In the following controls, slightly impaired kidney function was observed, indicating a progress of his chronic kidney disease (CKD).

Conclusion: Although leptospirosis is rare, there are some cases with a fulminant course. Impairment of renal function often correlates with severity of the disease requiring antibiotic treatment. In some cases, AKI progresses to CKD demonstrating the need to raise awareness for leptospirosis.

Missense variants in the PKHD1 gene are associated with the full spectrum of autosomal recessive polycystic kidney disease severity and exhibit variable expressivity. The study of clinical expressivity is limited by the extensive allelic heterogeneity within the PKHD1 gene, which encodes a 4074-amino-acid protein. We report the case of adult siblings with biallelic missense PKHD1 variants, c.4870C>T (p.Arg1624Trp) and c.8206T>G (p.Trp2736Gly), who presented with discordant phenotypes. Patient A developed progressive chronic kidney disease and Caroli syndrome in childhood requiring combined liver and kidney transplantation, while patient B remains minimally affected in the fourth decade of life with normal kidney function and signs of medullary sponge kidney on imaging. We review previously reported cases of phenotypic discordance among siblings and suggest that genotypes composed of at least one hypomorphic missense variant are more likely to lead to phenotypic discordance.

Introduction: C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury requiring continuous renal replacement therapy (CRRT).

Methods: We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results: In total, 3,995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all p < 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, p < 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, p = 0.003). CAR combined with Acute Physiology and Chronic Health Evaluation II or Sequential Organ Failure Assessment scores significantly increased the predictive power compared to each severity score alone for AUC, NRI, and IDI (all p < 0.05).

Conclusions: A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone.

Introduction: The regional variation in the use of percutaneous kidney biopsy in Japan remains unknown. There are several large datasets of kidney biopsies in Japan, but an exhaustive survey of kidney biopsies is lacking.

Methods: We analyzed insurance claims for percutaneous kidney biopsies registered in the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which is the closest to a complete dataset of kidney biopsies performed in Japan. In combination with other nationwide survey results, the number of inpatient percutaneous kidney biopsies per population in each prefecture was calculated. Factors associated with the frequency of percutaneous kidney biopsies were also explored.

Results: The database contained 22,419 health insurance claims for percutaneous kidney biopsy in the fiscal year 2020. The frequency of inpatient percutaneous kidney biopsies could be up to 4.8 times as frequent in one prefecture than in another, even after adjusting for age and sex. The frequency of inpatient percutaneous kidney biopsies showed a positive correlation with the number of annual kidney transplants and patients on peritoneal dialysis per population and a weak negative correlation with the prevalence of reduced kidney function in the population aged 40-74 years.

Conclusion: We found a large regional variation in the frequency of inpatient percutaneous kidney biopsies. Kidney transplants and peritoneal dialysis might be offered more frequently in regions with a higher frequency of kidney biopsy. This is the first dataset that shows more than 20,000 kidney biopsies were performed per year in Japan, as of 2020.