Current Opinion in Nephrology and Hypertension最新文献

Purpose of review: Despite a strong consensus that treatment of hypertension is fundamental to strategies seeking to slow chronic kidney disease (CKD) progression and reduce the associated risk of cardiovascular events (CVE), controversy persists regarding optimal blood pressure (BP) targets. This article reviews the evidence for different targets, discusses associated controversies and suggests approaches to improve BP control.

Recent findings: Landmark clinical trials established the principle that lower BP targets are associated with slower progression of CKD in people with a greater magnitude of proteinuria and previous guidelines recommended a target BP of <130/80 mmHg for those with proteinuria. However, the Systolic Blood Pressure Intervention Trial provided new evidence that a systolic BP target of <120 mmHg was associated with a reduced risk of CVE, though there was no impact on CKD progression and there was concern about an increase in renal adverse events. Nevertheless, 2021 Kidney Disease Improving Global Outcomes guidelines recommended systolic BP <120 mmHg, though other updated guidelines did not follow this trend. All guidelines emphasise the importance of standardised BP measurement and a personalised approach.

Summary: An individualised and shared decision-making approach to BP target setting and management is recommended, guided by standardised BP measurement.

Purpose of review: The opportunity to review the more recent evidence for prescribing exercise-based physical rehabilitation for people living with chronic kidney disease (CKD) is timely. There has been a recent global focus evaluating how physical activity interventions might improve health-related quality of life and outcomes for people living with chronic health conditions in a post-COVID era. There is finally a long overdue commitment from the kidney research and clinical community to deliver pragmatic interventions to help people living with CKD to be able to live well with their condition.

Recent findings: This article reviews recent research, and discusses the challenges and potential solutions, for providing exercise-based therapeutic options for people living with CKD; including predialysis self-management interventions, options for both prehabilitation and posttransplant rehabilitation, pragmatic considerations for delivery of exercise therapy for people receiving haemodialysis treatment and the role of virtual kidney-specific rehabilitation.

Summary: Whilst there remains a need for further research in this area of patient care, there is now a body of evidence and kidney-specific guidelines that firmly support a rollout of pragmatic and scalable exercise-based interventions for people living with CKD. We are indeed nearly there now.

Purpose of review: Patients with kidney disease were prioritized during COVID-19 vaccination efforts. Initial data on vaccine seroconversion and efficacy were confounded by heterogeneous vaccination regimens as well as response assessments. Recent data have addressed responses to evolving vaccine regimens, and addressed concerns in this high-risk population.

Recent findings: mRNA vaccines BNT162b2 (Pfizer/BioNTech), mRNA1273 (Moderna) were the predominant vaccines used in two and three-dose regimens. Although population-based studies show reduced rates of seroconversion in kidney disease cohorts, there continues to be evolving efficacy largely due to emerging variants, and utilization of ongoing vaccine development. Recommendations on vaccination regimens now exclude use of monovalent mRNA vaccines, with bivalent vaccines are now the preferred effective vaccination. Individualization and adjustment of immunosuppressive drugs is recommended for maximal serological response in transplant recipients and patient with autoimmune kidney diseases.

Summary: Waning responses to initial vaccination regimen, as well as emerging variants of concern have resulted in multiple dose regimens being investigated in patient with kidney disease. Use of bivalent mRNA vaccine is now recommended for initial as well as subsequent vaccine doses.

Purpose of review: In the past, the treatment of IgA nephropathy (IgAN), which is the most common glomerulonephritis worldwide, mostly relied on blockade of the renin-angiotensin system as a central component of so-called supportive therapy as well as on high-dose systemic corticosteroid therapy.

Recent findings: The supportive treatment arm has been expanded by the addition of sodium-glucose cotransporter-2 inhibitors, hydroxychloroquine, and, most recently, endothelin A receptor blockers. Treatment with high-dose systemic corticosteroids has become more controversial, with some studies observing no benefit and others documenting the protection of kidney function. However, all recent studies on systemic corticosteroids consistently found significant toxicity. An important novel approach to IgAN, therefore, is therapy with a targeted release formulation of budesonide with preferential release in the distal small intestine, given the mounting evidence for a gut-kidney axis in the pathophysiology of IgAN. In addition, emerging new therapeutic options include a variety of complement inhibitors as well as agents targeting B-cell proliferation and differentiation.

Summary: In recent years, IgAN has become the focus of a considerable number of clinical studies that will significantly advance the development of new therapy strategies.

Purpose of review: Tissue clearing enables examination of biological structures at subcellular resolution in three dimensions. It uncovered the spatial and temporal plasticity of multicellular kidney structures that occur during homeostatic stress. This article will review the recent development in tissue clearing protocols and how it facilitated the study of renal transport mechanisms and remodelling of the kidney.

Recent findings: Tissue clearing methods have evolved from primarily labelling proteins in thin tissue or individual organs to visualizing both RNA and protein simultaneously in whole animals or human organs. The use of small antibody fragments and innovative imaging techniques improved immunolabelling and resolution. These advances opened up new avenues for studying organ crosstalk and diseases that affect multiple parts of the organism. Accumulating evidence suggests that tubule remodelling can occur rapidly in response to homeostatic stress or injury, allowing for adjustments in the quantitative expression of renal transporters. Tissue clearing helped to better understand the development of tubule cystogenesis, renal hypertension and salt wasting syndromes, and revealed potential progenitor cells in the kidney.

Summary: The continued evolution and improvement of tissue clearing methods can help to gain deep biological insights into the structure and function of the kidney, which will have clinical implications.

Purpose of review: Kidney stone disease is caused by supersaturation of urine with certain metabolites and minerals. The urine composition of stone formers has been measured to prevent stone recurrence, specifically calcium, uric acid, oxalate, ammonia, citrate. However, these minerals and metabolites have proven to be unreliable in predicting stone recurrence. Metabolomics using high throughput technologies in well defined patient cohorts can identify metabolites that may provide insight into the pathogenesis of stones as well as offer possibilities in therapeutics.

Recent findings: Techniques including 1H-NMR, and liquid chromatography paired with tandem mass spectroscopy have identified multiple possible metabolites involved in stone formation. Compared to formers of calcium oxalate stones, healthy controls had higher levels of hippuric acid as well as metabolites involved in caffeine metabolism. Both the gut and urine microbiome may contribute to the altered metabolome of stone formers.

Summary: Although metabolomics has offered several potential metabolites that may be protective against or promote stone formation, the mechanisms behind these metabolomic profiles and their clinical significance requires further investigation.

Purpose of review: Several drugs cause nephrotoxicity and accelerate progression of chronic kidney disease (CKD). The objective of this review is to summarize recent evidence on drugs that either increase the risk of nephrotoxicity, progression of CKD or drug induced harm in patients with CKD.

Recent findings: Bisphosphonates and hypnotics increase the progression of CKD, whereas denosumab does not accelerate progression of CKD. Tenofovir disoproxil fumarate (TDF) increases the risk of renal tubular toxicity and adverse effects on bone, but Tenofovir alafenamide (TAF) and Tenofovir amibufenamide (TMF) have favorable safety profile on the kidneys and bones. Although no dosage adjustment is needed for Oral Nirmatrelvir/Ritonavir in patients with mild renal impairment and coronavirus disease 2019, the dosage is reduced to twice daily in those with moderate renal impairment. It is not recommended in patients with severe renal impairment. The prescribing information does not recommend use of remdesevir below glomerular filtration rate (eGFR) < 30 ml/min but recent studies suggest that remdesevir may be safe and effective in patients with varying levels of CKD severity. Molnupiravir does not require dose adjustment in patients with CKD.

Summary: Several medications increase the risk of development of acute kidney injury or progression of CKD. Close attention is needed to select the appropriate dose or safer alternatives to reduce the risk of drug-induced harm in patients with CKD.

Purpose of review: Renal denervation represents a new dimension to hypertension treatment, with multiple device manufacturers seeking premarket FDA approval currently. Interest in the efficacy and safety of the treatment has spurred compelling mechanistic studies into the function of renal nerves and downstream impacts of denervation.

Recent findings: A trial of the ultrasound Paradise Catheter system (RADIANCE II) found a 6.3 mmHg reduction in SBP relative to sham controls. A trial of the Symplicity Spyral system (SPYRAL HTN-ON MED) found an insignificant reduction in SBP relative to sham controls. Individuals were taking antihypertensive medications during the study, and investigators note the sham group experienced a larger medication burden than the denervated group. Recent preclinical studies have evaluated potential risks of renal denervation, how sympathetic activity broadly is affected, as well as identifying possible biomarkers to identify individuals where denervation would be more successful.

Summary: Studies of renal denervation continue to find a robust antihypertensive effect, especially in studies wherein medications are withdrawn. Further investigation into mechanisms and indicators for usage of the technique will be important in identifying the patient population most likely to benefit from usage of renal denervation.