Nephrology Dialysis Transplantation最新文献

While the native arteriovenous fistula remains the first choice in vascular access for most haemodialysis patients, tunnelled haemodialysis catheters (tHDCs) continue to be an option in selected patients. Since timely access to vascular surgery-due to delayed referral or resource limitations-is not always possible, nephrologists have to become more actively involved in planning, creation and monitoring of vascular access. Moreover, this approach could also strengthen patient-centred care in nephrology. This article reviews the current standard in tHDC creation, patient selection and strategies to mitigate the risk of infectious complications and catheter thrombosis. Presentation of novel developments in catheter placement with ultrasound-guided or electrocardiogram-guided positioning, their benefits and possible disadvantages emphasizes the complexity of vascular access planning. We offer an approach for the choice of insertion method, depending on selected side and existing resources and focus on the necessity and required resources of 'interventional nephrology' training programs.

Monogenic kidney diseases result from an abundance of potential genes carrying pathogenic variants. These conditions are primarily recognized for manifesting as kidney disorders, defined as an impairment of the structure and/or function of the kidneys. However, the impact of these genetic disorders extends far beyond the kidneys, giving rise to a diverse spectrum of extrarenal manifestations. These manifestations can affect any organ system throughout the body, leading to a complex clinical presentation that demands a comprehensive understanding and interdisciplinary management of affected persons. The intricate interplay between genetic variants, molecular pathways, and systemic interactions underscores the importance of exploring the extrarenal aspects of inherited kidney diseases. This exploration not only deepens our comprehension of the diseases themselves but also opens avenues for more holistic diagnostics, treatment strategies, and improved interdisciplinary patient care. This article delves into the intricate realm of extrarenal manifestations in inherited kidney diseases, shedding light on the far-reaching effects that these genetic conditions can exert beyond the confines of the kidney system.

Background: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes.

Methods: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200-≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<90 ml/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin system inhibitor were randomized 1:1 to once-daily placebo or finerenone 10 or 20 mg depending on eGFR >60 or <60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety.

Results: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium-glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline.

Conclusions: FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

The proximal tubule (PT) is known as the workhorse of the kidney, for both the range and magnitude of the functions that it performs. It is not only responsible for reabsorbing most solutes and proteins filtered by glomeruli, but also for secreting non-filtered substances including drugs and uremic toxins. The PT therefore plays a pivotal role in kidney physiology and body homeostasis. Moreover, it is the major site of damage in acute kidney injury and nephrotoxicity. In this review, we will provide an introduction to the cell biology of the PT and explore how it is adapted to the execution of a myriad of different functions and how these can differ between males and females. We will then discuss how the PT regulates phosphate, glucose and acid-base balance, and the consequences of alterations in PT function for bone and cardiovascular health. Finally, we explore why the PT is vulnerable to ischemic and toxic insults, and how acute injury in the PT can lead to maladaptive repair, chronic damage and kidney fibrosis. In summary, we will demonstrate that knowledge of the basic cell biology of the PT is critical for understanding kidney disease phenotypes and their associated systemic complications, and for developing new therapeutic strategies to prevent these.

Background: Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea.

Methods: This was a retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium <135 mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed.

Results: We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as the only treatment in 27 treatment episodes (17%). A median dose of 30 g/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134 mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (β 0.09, 95% CI 0.02-0.16), lower baseline plasma sodium (β -0.65, 95% CI -0.78 to -0.62) and higher cumulative urea dose (β 0.03, 95% CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48 h of treatment (β 1.81, 95% CI 0.40-3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified and oral urea was discontinued in 11 cases (11%) due to side effects.

Conclusion: During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.

Background: The association between superimposed preeclampsia and an elevated risk of long-term kidney function decline or end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) has not been determined. This study aimed to analyze the association between preeclampsia and kidney function deterioration in CKD patients.

Methods: This was a retrospective cohort study that included the clinical information of 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia who were followed-up for a minimum of 1 year after their first pregnancy from 1 January 2009 to 31 May 2022. Robust Cox regression analysis was also conducted to evaluate the effects of preeclampsia on long-term kidney function decline or ESKD in CKD patients. Kaplan-Meier curves were used to compare renal survival within different subgroups via the log-rank test.

Results: During the follow-up period, 44 (42.72%) CKD patients with preeclampsia and 20 (19.42%) without preeclampsia had an estimated glomerular filtration rate (eGFR) decrease >30% or developed ESKD. Compared with CKD patients without preeclampsia, the eGFR decreased more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs 99.43 (79.00, 118.50) to 89.44 (63.69, 105.30) mL/min/1.73 m2; P = .034]. The rate of eGFR decrease was more pronounced in patients with preeclampsia (17.38% vs 10.05%, P < .05). Multivariate analysis revealed that early-onset preeclampsia (preeclampsia that developed before 34 weeks of gestation) [hazard ratio (HR) = 2.61, 95% confidence interval (CI) 1.32-5.16, P = 0.006] and late-onset preeclampsia (HR = 2.54, 95% CI 1.34-4.83, P = .004) were both risk factors for an eGFR decrease >30% or ESKD.

Conclusion: Preeclampsia was associated with a greater risk of long-term kidney function decline or ESKD among CKD patients, especially in patients with early-onset preeclampsia.

True linear relationships are rare in clinical data. Despite this, linearity is often assumed during analyses, leading to potentially biased estimates and inaccurate conclusions. In this introductory paper, we aim to first describe-in a non-mathematical manner-how to identify non-linear relationships. Various methods are then discussed that can be applied to deal with non-linearity, including transformations, polynomials, splines and generalized additive models, along with their strengths and weaknesses. Finally, we illustrate the use of these methods with a practical example from nephrology, providing guidance on how to report the results from non-linear relationships.

Background: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with haemodialysis (HD) or peritoneal dialysis (PD).

Methods: We studied adults ≥20 years of age in Alberta, Canada receiving maintenance HD or PD as of 31 March 2019. We characterized participants as users of 0-29 drug categories of interest and those ≥65 years of age as users/non-users of potentially inappropriate medications (PIMs). We calculated the number of drug categories, daily pill burden, total annual cost and annual cost per participant and compared this to an age- and sex-matched cohort from the general Alberta population.

Results: Among 2248 participants (mean age 63 years; 39% female) on HD (n = 1781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4-8] and the median daily pill burden was 8.0 (IQR 4.6-12.6), with 5% prescribed ≥21.7 pills/day and 16.5% prescribed ≥15 pills/day. Twelve percent were prescribed at least one drug that is contraindicated in kidney failure. The median annual per-participant cost was ${$}$3831, totalling ≈${$}$11.6 million annually for all participants. When restricting to the 1063 participants ≥65 years of age, the median number of PIM categories was 2 (IQR 1-2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5-2.4). Compared with PD participants, HD participants had a similar daily pill burden, higher use of PIMs and higher annual per-participant cost. Pill burden and associated costs for participants on dialysis were >3-fold and 10-fold higher, respectively, compared with the matched participants from the general population.

Conclusion: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed.