American Journal of Nephrology最新文献

Introduction: Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety.

Methods: We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause.

Results: Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (RR, 0.32; 95%CI, 0.13 to 0.77), reducing proteinuria (RR, 1.41; 95%CI, 1.22 to 1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14 to 0.72). No significant differences were detected in the incidence of ESRD (RR: 0.87, 95% CI: 0.38 to 2.03), or progression of chronic kidney disease (RR, 1.01; 95%CI, 0.22 to 4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95%CI, 1.21 to 4.00).

Conclusion: MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still needs need further cross-regional and cross-ethnical verification.

Introduction: The role of dietary sodium intake in the risk of CKD progression remains controversial. This study aimed to evaluate the association of urinary sodium excretion and progression of IgA nephropathy.

Methods: We assessed 596 patients with IgA nephropathy, urinary sodium excretion was measured at the time of kidney biopsy. Cox proportional hazards models and restricted cubic splines were used to assess the association between urinary sodium excretion and kidney disease progression events, defined as 50% eGFR decline or development of kidney failure.

Results: After a mean follow-up of 58.9 months, a total of 75 (12.6%) participants of IgA nephropathy reached composite kidney disease progression events. The risk of kidney disease progression events was higher in patients with higher urinary sodium excretion. After adjustment for traditional risk factors, higher levels of ln transformed urinary sodium excretion was associated with the kidney disease progression events in patients with IgA nephropathy (HR, 2.1; 95% CI, 1.4-3.2). In reference to the first tertile of urinary sodium excretion, hazard ratios were 1.9 (95% CI, 1.0-3.4) for the second tertile, 2.1 (95% CI, 1.1-3.9) for the third tertile.

Conclusion: Higher levels of urinary sodium excretion were associated with kidney disease progression events in IgA nephropathy independent of clinical and biopsy characteristics.

Introduction: Worsening renal function poses a significant health risk to elderly individuals. This study aimed to construct a simple risk prediction model for new-onset chronic kidney disease (CKD) among elderly populations.

Methods: In this retrospective cohort study, 5,416 elderly residents (aged ≥ 65 years) who underwent physical examinations as part of the National Basic Public Health Service project at least twice between January 2017 and July 2021 were included. The endpoint was new-onset CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² during the follow-up period. Predictors of new-onset CKD were selected using multivariable Cox regression and a stepwise approach. A risk prediction model based on the selected predictors was constructed and evaluated using the concordance index (C-index) and area under curve (AUC). External validation was conducted to verify the model's performance.

Results: During the median follow-up period of 2.3 years, the incident of new-onset CKD was 20.1% (n = 1,088). Age, female gender, diabetes, elevated triglyceride levels, and baseline eGFR were selected as predictors. The model demonstrated good predictive performance across the cohort, with a C-index of 0.802. The AUCs for 2-year, 3-year, and 4-year predictions were 0.831, 0.829, and 0.839, respectively. External validation confirmed the model's efficacy, with a 2-year AUC of 0.735.

Conclusion: This study developed a simple yet effective risk prediction model for new-onset CKD among elderly populations. The model facilitates prompt identification of elderly individuals at risk of renal function decline in primary care, enabling timely interventions.

Introduction Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). Methods Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL). Results A total of 157 patients were enrolled, of whom 138 completed the study. Overall, 94.2% of patients achieved the target serum iPTH level at week 52. Neither symptomatic hypocalcemia nor cCa level <7.5 mg/dL occurred despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Upacicalcet improved the control of serum phosphate (P) and calcium levels regardless of baseline PTH levels and decreased intact fibroblast growth factor-23 levels. The largest parathyroid glands shrank, irrespective of their baseline volume or prior calcimimetic usage. Upacicalcet was well-tolerated, with no adverse events requiring dose reduction. Conclusion This is the first study to show that a calcimimetic improves serum P and cCa control without inducing severe hypocalcemia in patients with iPTH levels ≤300 pg/mL. Upacicalcet is efficacious in HD patients with mild-to-severe SHPT, with few safety concerns.

Introduction: The optimal time for vascular access (VA) creation remains controversial.

Methods: We conducted a cohort study using data from the Japanese Society for Dialysis Therapy Renal Data Registry. Adult patients who started receiving hemodialysis in 2007 and had a permanent VA created were included. The exposure of interest was the timing of VA creation, categorized into three groups: early VA creation (defined as creation at least 4 months before hemodialysis initiation), just prior VA creation (creation between 1 and 3 months before hemodialysis initiation), and late VA creation (creation within 1 month of or after hemodialysis initiation). Cox regression analyses were used to compare 1-year all-cause mortality, with late VA creation as the reference group. Owing to the violations of the proportional hazards assumptions, the follow-up period was divided into 'early' (1-4 months follow-up) and 'late' (5-12 months follow-up) periods.

Results: Overall, 1,280 (15.4%) of 8,322 patients died. Both early creation and just prior creation were associated with lower all-cause mortality in the early period compared with late creation. In the late period, the hazard ratios (HRs) for all-cause mortality decreased with earlier VA creation (adjusted HRs [95% confidence intervals]: 0.49 [0.35-0.67] for the early creation group and 0.63 [0.51-0.79] for the just prior creation group).

Conclusion: Our study suggests that VA creation at least 1 month before hemodialysis initiation is associated with lower all-cause mortality in the early period, with earlier VA creation resulting in further mortality reduction in the late period.

Introduction: Vitamin D insufficiency is common in patients who receive hemodialysis, yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP).

Methods: Baseline 25(OH)D3 level was measured in all patients receiving in-center hemodialysis in June 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February 2021. In September 2018, a treatment algorithm of 50,000 IU weekly until sufficient followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP, and PTH.

Results: Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 <25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7,272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. Overall, 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range.

Conclusions: Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in clinical endpoints warrants further study.

Introduction: The aim of the study was to explore the causes and clinical significance of hyperechoic renal medulla observed by ultrasonography in patients with primary gout.

Methods: This study included 2,107 patients with primary gout treated in the Gout Clinic of our hospital from 2016 to 2022. The clinical data and biochemical data of these patients were collected and analyzed. According to the presence or absence of punctate hyperechogenicity in the renal medulla on ultrasound examination, the patients were divided into the hyperechoic medulla (HM) and the normal hypoechoic medulla (NM) groups, and the HM group was further divided into the partial HM (P-HM) and fulfilled HM (F-HM) subgroups according to the distribution range of hyperechogenicity.

Results: Among the 2,107 patients with primary gout, 380 had hyperechoic renal medulla on renal ultrasound, including 106 patients with F-HM and 274 with P-HM. There were significant differences in the gout duration, urate arthropathy number, serum urate (SU) level, clinical tophi number, blood urea nitrogen, serum creatinine (sCr), and estimated glomerular filtration rate between the HM and NM groups or between the F-HM and P-HM subgroups (p < 0.05). Multivariate regression analysis showed that the presence of HM was positively correlated with gout duration, urate arthropathy number, gout attack frequency, SU, and sCr. The number of clinical tophi and sCr were closely related to F-HM.

Conclusion: Ultrasound examination showed that a high medulla echo in patients with gout was often related to renal function damage. P-HM may be a transitory condition between NM and F-HM in patients with gout.

Introduction: Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline.

Methods: Changes in estimated glomerular filtration rate (eGFR) were analyzed post hoc in 126 adults with SHPT, stage 3-4 CKD, and low serum 25-hydroxyvitamin D (25D) treated for 1 year with ERC in pivotal trials. ERC was administered at 30 μg/day increasing, as needed, to 60 μg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor-23 (FGF23), bone turnover markers (BTMs), and urine albumin-to-creatinine ratio (uACR) were measured at baseline and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline.

Results: For all participants, 25D increased 58.5 ± 2.3 (SE) ng/mL (p < 0.001) by the end of treatment (EOT), 1,25D increased 10.1 ± 1.8 pg/mL (p < 0.001), iPTH decreased from 143.8 ± 5.8 pg/mL to 108.8 ± 7.2 (p < 0.001), BTMs improved (p < 0.01), and eGFR declined 2.2 ± 0.5 mL/min/1.73 m2 (p < 0.001). The rate of eGFR decline was >5-fold higher (p = 0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2 ± 0.7; 12.7 ± 2.2%) than in those who did (0.6 ± 0.8; 2.9 ± 2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4 ± 0.9; 20.9 ± 3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression.

Conclusion: Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3-4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.

Introduction: Cardiovascular health disparities are present within several minority communities, but it is unclear if such disparities are present in a growing African American subpopulation, Somali Americans, who differ genetically and culturally from African Americans of Western African ancestry. Ambulatory blood pressure (BP) monitoring remains a gold standard measure to examine 24-h BP patterns to stratify cardiovascular risk profile. We sought to examine differences in the 24-h BP profile in a sample of young Somali Americans and compare their BP patterns to White study participants. We hypothesized that their BP and heart rate (HR) would be higher compared to closely matched White participants.

Methods: We recruited 50 participants (25 Somali) in whom BP recordings were obtained every 20 min throughout the entire 24-h monitoring period to quantify BP, HR, and ambulatory arterial stiffness. Daytime BP/HR was quantified between 10:00 a.m. and 8:00 p.m., and nighttime BP/HR was assessed between 12:00 a.m. and 6:00 a.m.

Results: Daytime BP and HR were similar between racial groups (p > 0.05). Nighttime BP was similar between groups (p > 0.05), but Somali American individuals exhibited a higher nocturnal HR compared to White participants (p = 0.013). Nocturnal dipping in diastolic BP and HR dipping was attenuated in Somali Americans compared to White adults (p = 0.038, 0.007). Somali participants also had higher ambulatory arterial stiffness (p = 0.045).

Conclusion: Twenty four-hour hemodynamics, specifically ambulatory arterial stiffness, nocturnal BP, and nocturnal HR, differ in young Somali Americans compared to White adults. These findings provide new insight into potential cardiovascular health disparities and future cardiovascular risk within the burgeoning Somali American community.

Introduction: Chronic kidney disease (CKD) can have a profound impact on patients' lives. However, multinational data on patients' lived experience with CKD are scarce.

Methods: Individuals from the prospective cohort of DISCOVER CKD (NCT04034992), an observational cohort study, were recruited to participate in one-to-one telephone interviews to explore their lived experience with CKD. A target of 100 participant interviews was planned across four countries (Japan, Spain, the UK, and the USA). These qualitative interviews, lasting ∼60-90 min, were conducted in the local language by trained interviewers with specific experience in CKD, between January and June 2023. Transcribed interviews were translated into English for coding and analysis. Data were coded using qualitative research software.

Results: Of the 105 participants interviewed, 103 were included in the final analysis. The average time since CKD diagnosis was 9.5 years, and at least half (50.5%) of participants had CKD stage 3A or 3B. CKD diagnosis was an emotional experience, driven by worry (n = 29/103; 28.2%) and shock (n = 26/103; 25.2%), and participants often reported feeling inadequately informed. Additional information was frequently sought, either online or via other healthcare providers. The proportion of participants reporting no impacts of CKD on their lives was highest in those with CKD stage 1 and 2 (64.3%). Conversely, every participant in the CKD stage 5 on dialysis group reported some impact of CKD on their lives. Across all participants, the most reported impacts were anxiety or depression (37.9%) or ability to sleep (37.9%). The frequency of the reported impacts appeared to increase with disease severity, with the highest rates observed in the dialysis group. In that group, the most frequently reported impact was on the ability to work (80.0%).

Conclusion: Findings from this multinational qualitative study suggest that patients may experience symptoms and signs of disease prior to diagnosis; however, these are often nonspecific and may not be directly associated with CKD. Once diagnosed, the burden of CKD can have a diverse, negative impact on various aspects of patients' lives. This highlights the need for early identification of at-risk individuals, and the importance of early CKD diagnosis and management with guideline-directed therapies to either prevent further deterioration of CKD or slow its progression, thus reducing symptom burden and improving quality of life.