Nephron最新文献

{"title":"Techniques to Assess the Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Blood Volume in Patients with Diabetic Kidney Disease.","authors":"Vårin Vinje, Tobias Bomholt, Peter Rossing, Carsten Lundby, Peter Oturai, Mads Hornum","doi":"10.1159/000534396","DOIUrl":"10.1159/000534396","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects.</p><p><strong>Summary: </strong>Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated.</p><p><strong>Key messages: </strong>A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"137-142"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41183178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penehyclidine Hydrochloride Improves Rhabdomyolysis-Mediated Acute Kidney Injury by Inhibiting Ferroptosis through the HIF-1α/MT1G Axis.","authors":"Li Chen, ShaSha Luo, HongBao Tan","doi":"10.1159/000534393","DOIUrl":"10.1159/000534393","url":null,"abstract":"<p><strong>Background: </strong>Penehyclidine hydrochloride (PHC) has been shown to be effective in the treatment of rhabdomyolysis (RM)-induced acute kidney injury (AKI). Our research sought to investigate the pharmacological effects and mechanisms of PHC on RM-induced AKI.</p><p><strong>Methods: </strong>RM-induced AKI models were established by FeG treatment and glycerol injection. Cell viability was analyzed by cell counting kit-8 assay. Reactive oxygen species (ROS) levels were examined by flow cytometry. The LDH, Fe2+, MPO, MDA, and GSH levels were measured using the corresponding kits. The interaction between HIF-1α and MT1G was analyzed by dual-luciferase reporter gene and chromatin immunoprecipitation assays. The kidney pathological alterations were examined by hematoxylin-eosin staining. The levels of serum creatinine, uric acid, and blood urea nitrogen were examined using ELISA. Ferroptosis-related proteins (SLC7A11, GPX4, and ACSL4) were analyzed by Western blot.</p><p><strong>Results: </strong>PHC administration increased FeG-treated HK-2 cell viability, reduced ROS, LDH, Fe2+, MPO, MDA, and ACSL4 levels, and raised GSH, SLC7A11, and GPX4 levels in cells, suggesting that PHC improved FeG-induced HK-2 cell ferroptosis and injury. PHC protected against AKI primarily by suppressing ferroptosis. HIF-1α blocked the SLC7A11/GPX4 pathway by transcriptionally activating MT1G. PHC alleviated glycerol-induced kidney injury in rats by inhibiting ferroptosis.</p><p><strong>Conclusion: </strong>PHC improved RM-mediated AKI by inhibiting ferroptosis through the HIF-1α/MT1G/SLC7A11/GPX4 axis.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"333-344"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical and Mutational Spectrum of 69 Turkish Children with Autosomal Recessive or Autosomal Dominant Polycystic Kidney Disease: A Multicenter Retrospective Cohort Study.","authors":"Ozum Tutal, Bora Gulhan, Emine Atayar, Selcuk Yuksel, Z Birsin Ozcakar, Oguz Soylemezoglu, Seha Saygili, Salim Caliskan, Mihriban Inozu, Esra Baskin, Ali Duzova, Mutlu Hayran, Rezan Topaloglu, Fatih Ozaltin","doi":"10.1159/000528258","DOIUrl":"10.1159/000528258","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal recessive polycystic kidney disease (ARPKD) is associated with pathogenic variants in the PKHD1 gene. Autosomal dominant polycystic kidney disease (ADPKD) is mainly associated with pathogenic variants in PKD1 or PKD2. The present study aimed to identify the clinical and genetic features of Turkish pediatric ARPKD and ADPKD patients.</p><p><strong>Methods: </strong>This multicenter, retrospective cohort study included 21 genetically confirmed ARPKD and 48 genetically confirmed ADPKD patients from 7 pediatric nephrology centers. Demographic features, clinical, and laboratory findings at presentation and during 12-month intervals were recorded.</p><p><strong>Results: </strong>The median age of the ARPKD patients at diagnosis was lower than the median age of ADPKD patients (10.5 months [range: 0-15 years] vs. 5.2 years [range: 0.1-16 years], respectively, [p = 0.014]). At the time of diagnosis, the median eGFR in the ARPKD patients was lower compared to that of ADPKD patients (81.6 [IQR: 28.7-110.5] mL/min/1.73 m2 and 118 [IQR: 91.2-139.8] mL/min/1.73 m2, respectively, [p = 0.0001]). In total, 11 (52.4%) ARPKD patients had malnutrition; 7 (33.3%) patients had growth retardation at presentation; and 4 (19%) patients had both malnutrition and growth retardation. At diagnosis, 8 (16.7%) of the ADPKD patients had malnutrition, and 5 (10.4%) patients had growth retardation. The malnutrition, growth retardation, and hypertension rates at diagnosis were higher in the ARPKD patients than the ADPKD patients (p = 0.002, p = 0.02, and p = 0.0001, respectively). ARPKD patients with malnutrition and growth retardation had worse renal survival compared to the patients without (p = 0.03 and p = 0.01). Similarly, ADPKD patients with malnutrition had worse renal survival compared to the patients without (p = 0.002). ARPKD patients with truncating variants had poorer 3- and 6-year renal outcome than those carrying non-truncating variants (p = 0.017).</p><p><strong>Conclusion: </strong>Based on renal survival analysis, type of genetic variant, growth retardation, and/or malnutrition at presentation were observed to be factors associated with progression to chronic kidney disease (CKD). Differentiation of ARPKD and ADPKD, and identification of the predictors of the development of CKD are vital for optimal management of patients with ARPKD or ADPKD.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"319-332"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10548860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-Occurrence of Nephronophthisis Type 1 and Alström Syndrome: A Case Report.","authors":"Lisa Rossoni, Francesca Lugani, Silvia Maria Orsi, Enrico Eugenio Verrina, Gian Marco Ghiggeri, Andrea Angeletti, Gianluca Caridi, Edoardo La Porta","doi":"10.1159/000529473","DOIUrl":"10.1159/000529473","url":null,"abstract":"<p><p>We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: nephronophthisis type 1 (NPHP1) and Alström syndrome (AS). NPHP1 is one of the main genetic causes of terminal kidney failure in childhood. AS is an ultra-rare multi-systemic disease, characterized by progressive kidney disease, hepatic failure, dystrophy of the rods and cones to blindness, slowly progressive neuro-sensory deafness, dilated cardiomyopathy, obesity, insulin resistance/type 2 diabetes mellitus. The coexistence in the same patient of two rare syndromes with overlapping clinical manifestations but genetically different is an eventuality to be considered. This case report would describe the onset and progression of the multi-organ manifestations of both syndromes to highlight that ciliopathies present a strong phenotype overlap but also specific peculiarities. Therefore, to make a correct diagnosis that is essential to achieve the best clinical management could be challenging.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"345-348"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10660652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association between High-Dose Allopurinol and Erythropoietin Hyporesponsiveness in Advanced Chronic Kidney Disease: JOINT-KD Study.","authors":"Megumi Oikawa, Hiroki Nishiwaki, Takeshi Hasegawa, Sho Sasaki, Masahiko Yazawa, Hitoshi Miyazato, Yosuke Saka, Hideaki Shimizu, Yoshiro Fujita, Minoru Murakami, Daisuke Uchida, Hiroo Kawarazaki, Shinya Omiya, Fumihiko Sasai, Fumihiko Koiwa","doi":"10.1159/000535874","DOIUrl":"10.1159/000535874","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5.</p><p><strong>Methods: </strong>We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (&gt;50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs.</p><p><strong>Results: </strong>A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10-3.57).</p><p><strong>Conclusions: </strong>Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"448-456"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirect Markers of Intestinal Damage in IgA Nephropathy.","authors":"Jussi Pohjonen, Katri Kaukinen, Heini Huhtala, Ilkka Pörsti, Katri Lindfors, Jukka Mustonen, Satu Mäkelä","doi":"10.1159/000538242","DOIUrl":"10.1159/000538242","url":null,"abstract":"<p><strong>Introduction: </strong>Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN.</p><p><strong>Methods: </strong>Eighty-five primary IgAN patients (median age 55 years, 54% men) participated in this single-center study in Tampere, Finland. None had end-stage kidney disease or previously diagnosed enteropathies. Celiac disease was excluded with serum transglutaminase 2 antibody (TG2Ab) and endomysial antibody tests and inflammatory bowel disease with fecal calprotectin. Intestinal damage was evaluated from sera with analyses of intestinal fatty-acid binding protein (I-FABP), soluble cluster of differentiation molecule 14 (sCD14), and lipopolysaccharide binding protein. Fourteen people suffering from dyspepsia and 15 healthy people served as controls.</p><p><strong>Results: </strong>I-FABP levels among IgAN patients were higher than in the healthy controls (median 830 pg/mL vs. 289 pg/mL, p &lt; 0.001). Also, sCD14 was increased in IgAN patients compared to dyspepsia controls. Although TG2Ab levels were within the normal range among IgAN patients, they were higher than in the healthy controls (median 1.3 U/mL vs. 0.6 U/mL, p &lt; 0.001).</p><p><strong>Conclusions: </strong>Elevated serum levels of I-FABP were present in primary IgAN patients without known enteropathies. Serum I-FABP may indicate the presence of subclinical intestinal damage. These findings encourage further investigation into the role of the intestine in the pathophysiology of IgAN.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"693-700"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-874-3p Is Identified as a Biomarker for Acute Kidney Injury and Mediates Disease Development via Targeting MSRB3.","authors":"Jun Ge, Xuefeng Zhang, Ye Liu, Hang Liu, Xiaoming Liu","doi":"10.1159/000534842","DOIUrl":"10.1159/000534842","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>miR-874-3p served as a diagnostic and prognostic biomarker of AKI and mediate the severity and development of AKI via targeting MSRB3.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"426-436"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pathophysiology of Left Ventricular Hypertrophy, beyond Hypertension, in Autosomal Dominant Polycystic Kidney Disease.","authors":"Ozgur A Oto, Charles L Edelstein","doi":"10.1159/000525944","DOIUrl":"10.1159/000525944","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"215-223"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Exercise on Metabolic and Renal Outcomes in Patients with Chronic Kidney Disease: A Narrative Review.","authors":"Raúl Morales Febles, Domingo Marrero Miranda, Coriolano de la Concepción Cruz Perera, Laura Díaz Martín, Ana Elena Rodríguez-Rodríguez, Amelia Remedios González Martín, Daniel Javier Sánchez Báez, Esteban Porrini","doi":"10.1159/000531921","DOIUrl":"10.1159/000531921","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"85-94"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10058550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Complexity of Decisions in Genetics: Annotation of Three Novel Variants in the PKD1 and PKD2 Genes.","authors":"Rui Barata, Liliana Rocha, Isabel Tavares, Odete Pereira, Filipa Carvalho, João Paulo Oliveira","doi":"10.1159/000534969","DOIUrl":"10.1159/000534969","url":null,"abstract":"<p><p>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&gt;G, p.(Leu117Val) and c.1736C&gt;T, p.(Pro579Leu); and the third in the PKD2 gene - c.1124A&gt;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&gt;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.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"503-507"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}