Current Opinion in Nephrology and Hypertension最新文献

Purpose of review: In this report, we summarize why the availability of cystatin C is important across a variety of clinical scenarios, the recent literature on when, why and in whom cystatin C testing should be considered, and how nephrologists can take practical steps to incorporate cystatin C testing into their practice.

Recent findings: Large intra-individual discrepancies between estimated glomerular filtration rate by creatinine (eGFRcr) and estimated glomerular filtration rate by creatinine eGFRcys (known as eGFRdiff) are observed in at least 1 in 4 people. These differences are seen more commonly among more vulnerable individuals: older adults, females, non-White individuals and those living with multiple medical conditions. A large eGFRdiff, where eGFRcys is lower than eGFRcr, is associated with a plethora of adverse outcomes, including medication-associated adverse events, acute kidney injury, cardiovascular disease, kidney failure and all-cause mortality. Among studies that have measured GFR, eGFRcr-cys usually provides the most accurate estimation of kidney function compared to mGFR, including among participants with large discrepancies between eGFRcr and eGFRcys.

Summary: Cystatin C improves sensitivity and specificity of chronic kidney disease diagnosis, improves detection of harmful acute and chronic changes in kidney function, improves precision of treatment eligibility and safety, and may reduce healthcare inequalities. Better education, curiosity, and motivation among nephrologists could substantially improve the availability and utilization of cystatin C.

Purpose of review: With the latest classification, variants in three collagen IV genes, COL4A3 , COL4A4 , and COL4A5 , represent the most prevalent genetic kidney disease in humans, exhibiting diverse, complex, and inconsistent clinical manifestations. This review breaks down the disease spectrum and genotype-phenotype correlations of kidney diseases linked to genetic variants in these genes and distinguishes "classic" Alport syndrome (AS) from the less severe nonsyndromic genetically related nephropathies that we suggest be called "Alport kidney diseases".

Recent findings: Several research studies have focused on the genotype-phenotype correlation under the latest classification scheme of AS. The historic diagnoses of "benign familial hematuria" and "thin basement membrane nephropathy" linked to heterozygous variants in COL4A3 or COL4A4 are suggested to be obsolete, but instead classified as autosomal AS by recent expert consensus due to a significant risk of disease progression.

Summary: The concept of Alport kidney disease extends beyond classic AS. Patients carrying pathogenic variants in any one of the COL4A3/A4/A5 genes can have variable phenotypes ranging from completely normal/clinically unrecognizable, hematuria without or with proteinuria, or progression to chronic kidney disease and kidney failure, depending on sex, genotype, and interplays of other genetic as well as environmental factors.

Purpose of review: Systemic lupus erythematosus (SLE) can be a devastating condition, striking young patients often in their prime reproductive years. Lupus nephritis is a common and serious complication occurring in roughly 50% of SLE cases, indicating a high likelihood of disease progression, morbidity, and mortality. As the early trials of steroid therapy, and later cyclophosphamide (CYC), therapeutic changes had been stagnant. Then came the introduction of mycophenolate mofetil (MMF) in the 2000s. After the Aspreva Lupus Management Study, there had been a dearth of trials showing positive therapy results. Since 2020, new studies have emerged for lupus nephritis involving the use of anti-BLYS agents, novel calcineurin inhibitors, CD20 blockade, and antiinterferon agents. Nephrology and rheumatology society guidelines in the United States and across the world are still catching up.

Recent findings: Although therapeutic guidelines are being developed, updates that have come through have focused on improved diagnostic and monitoring guidelines. One theme is the recommendation of increasingly tight proteinuria control and firmer guidelines for the rapid induction of remission. The reality of multitarget therapy and the expectation of rapid induction for a more complete remission are being widely recognized.

Summary: The need for more complete and more rapid induction and control of lupus nephritis is undisputed according to the evidence and guidelines, and the medications to achieve this are growing at a rate not seen over the prior two decades. What remains is a stepwise approach to recognize how to best optimize therapy. Based on available evidence, an algorithm for induction and maintenance treatment of lupus nephritis used by the University of California Irvine Lupus Nephritis clinic, is recommended.

Purpose of review: Diabetic kidney disease continues to increase, and several novel therapeutic agents have been shown to slow the progression of chronic kidney disease in those with diabetes. This review summarizes more recent data on the role of glucagon-like peptide-1 (GLP-1) receptor agonists and kidney outcomes.

Recent findings: Posthoc analysis of cardiovascular outcome trials, as well as several retrospective studies, demonstrate benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics. Although limited randomized clinical trials evidence assessing the effects of GLP-1 receptor agonists on kidney outcomes in diabetic chronic kidney disease patients have been published, FLOW-CKD trial was halted based on interim data for efficacy, and results are awaited.

Summary: GLP-1 receptor agonism is a promising therapy for slowing the progression of diabetic chronic kidney disease. Recent studies support kidney benefits GLP-1 receptor agonists over insulin and dipeptidyl peptidase-4-inhibitors, and the FLOW-CKD trial would inform the potential benefits for reducing the need for dialysis and kidney-disease related mortality in those with kidney disease.

Purpose of review: The conventional definition of chronic kidney disease (CKD) primarily relies on the identification of albuminuria or a decline in estimated glomerular filtration rate (eGFR). For many years, a straightforward eGFR threshold of <60 ml/min/1.73 m 2 has been widely adopted as the standard for defining CKD. Nonetheless, this criterion fails to consider the natural aging process of the kidney, and this oversight may affect the accurate diagnosis of kidney disease particularly at the extremes of age.

Recent findings: The fixed eGFR threshold of <60 ml/min/1.73 m 2 for defining CKD misses crucial opportunities for risk prevention. Studies have revealed that the eGFR threshold at which the risks for adverse long-term health outcomes such as mortality, cardiovascular events, and kidney failure begin to rise varies substantially by age. Specifically, this threshold is lower for the elderly and higher for young adults. Consequently, this results in the over-diagnosis of kidney disease in the elderly and the under-diagnosis of kidney disease in young adults.

Summary: To address these limitations of the current CKD definition, we discuss a number of proposed age-adapted eGFR criteria and weigh their pros and cons against the current, simple, and universally accepted approach.

Purpose of review: The last year has seen considerable progress in translational research exploring the clinical utility of biopsy-based transcriptomics of kidney transplant biopsies to enhance the diagnosis of rejection. This review will summarize recent findings with a focus on different platforms, potential clinical applications, and barriers to clinical adoption.

Recent findings: Recent literature has focussed on using biopsy-based transcriptomics to improve diagnosis of rejection, in particular antibody-mediated rejection. Different techniques of gene expression analysis (reverse transcriptase quantitative PCR, microarrays, probe-based techniques) have been used either on separate samples with ideally preserved RNA, or on left over tissue from routine biopsy processing. Despite remarkable consistency in overall patterns of gene expression, there is no consensus on acceptable indications, or whether biopsy-based transcriptomics adds significant value at reasonable cost to current diagnostic practice.

Summary: Access to biopsy-based transcriptomics will widen as regulatory approvals for platforms and gene expression models develop. Clinicians need more evidence and guidance to inform decisions on how to use precious biopsy samples for biopsy-based transcriptomics, and how to integrate results with standard histology-based diagnosis.

Purpose of review: To present findings indicating the value of kidney biopsy in assessing prognosis and guiding clinical approach to patients with IgA vasculitis nephritis (IgAVN), including a recent international study examining the value of the Oxford (MEST-C) classification.

Recent findings: Historically, kidney biopsies with IgAVN are scored using the International Society for Kidney Diseases in Children (ISKDC) classification. However, this classification has limited prognostic value, and most biopsies fall into just two of the six ISKDC grades. There are few studies examining the clinical value of the Oxford classification, which is well documented to be predictive of kidney outcomes in IgA nephropathy, in IgAVN. However, a recent study of 361 biopsied patients with IgAVN showed that endocapillary hypercellularity (Oxford E1) predicted a subclass of patients showing initial improvement in kidney function with immunosuppressive treatment, followed by a later decline.

Summary: Kidney outcome in patients with biopsied IgAVN treated with immunosuppression is determined by clinical factors and endocapillary hypercellularity. The latter is not part of the ISKDC classification and supports including MEST-C scores in biopsy reports of IgAVN. Even patients showing a good initial response to immunosuppression require long-term follow-up due to risk of subsequent kidney function decline.

Purpose of review: Kidney dysfunction is challenging in liver transplant candidates to determine whether it is reversible or not. This review focuses on the pertinent data on how to best approach liver transplant candidates with kidney dysfunction in the current era after implementing the simultaneous liver kidney (SLK) allocation policy and safety net.

Recent findings: The implementation of the SLK policy inverted the steady rise in SLK transplants and improved the utilization of high-quality kidneys. Access to kidney transplantation following liver transplant alone (LTA) increased with favorable outcomes. Estimating GFR in liver transplant candidates remains challenging, and innovative methods are needed. SLK provided superior patient and graft survival compared to LTA only for patients with advanced CKD and dialysis at least 3 months. SLK can provide immunological protection against kidney rejection in highly sensitized candidates. Post-SLK transplant care is complex, with an increased risk of complications and hospitalization.

Summary: The SLK policy improved kidney access and utilization. Transplant centers are encouraged, under the safety net, to reserve SLK for liver transplant candidates with advanced CKD or dialysis at least 3 months while allowing lower thresholds for highly sensitized patients. Herein, we propose a practical approach to liver transplant candidates with kidney dysfunction.

Purpose of review: Nephropathology is increasingly incorporating computational methods to enhance research and diagnostic accuracy. The widespread adoption of digital pathology, coupled with advancements in deep learning, will likely transform our pathology practices. Here, we discuss basic concepts of deep learning, recent applications in nephropathology, current challenges in implementation and future perspectives.

Recent findings: Deep learning models have been developed and tested in various areas of nephropathology, for example, predicting kidney disease progression or diagnosing diseases based on imaging and clinical data. Despite their promising potential, challenges remain that hinder a wider adoption, for example, the lack of prospective evidence and testing in real-world scenarios.

Summary: Deep learning offers great opportunities to improve quantitative and qualitative kidney histology analysis for research and clinical nephropathology diagnostics. Although exciting approaches already exist, the potential of deep learning in nephropathology is only at its beginning and we can expect much more to come.