American Journal of Nephrology最新文献

Introduction: Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, and edema, though not all patients present with edema. This study investigates edema prevalence and its association with venous thromboembolism, kidney failure, and mortality in patients with nephrotic-range albuminuria and hypoalbuminemia.

Methods: We conducted a Danish multicenter cohort study, including patients with plasma albumin <30 g/L and nephrotic-range albuminuria in the Central Denmark Region (2012-2022). Patients were identified using the laboratory information system and followed until death, lost to follow-up, or end of study. Data on demographics, comorbidities, biochemical markers, medical treatment, renal pathology, edema, venous thromboembolism, bleeding, kidney failure, and death were collected.

Results: Among 1,219 patients, 758 (62%) had edema at diagnosis. Patients with edema had a higher urine albumin creatinine ratio (4245 mg/g [3046-6079] vs. 3546 mg/g [2691-5125]) or a higher 24-hour urine albumin excretion rate (4559 mg/day [3146-6591] vs. 3546 mg/day [2828-5578]) and lower plasma albumin (26 g/l [22-28] vs. 28 g/l [26-29]) than those without edema. Venous thromboembolism occurred in 54 (4%) patients, with an incidence rate of 15 (95% CI, 11-21) per 1000 person-years in patients with edema vs. 10 (95% CI, 10-17) in patients without. Edema was also associated with faster kidney failure progression (edema: 188 days (IQR, 28-581); non-edema: 364 days (IQR, 116-920)) and higher one-year all-cause mortality (edema: 19%; non-edema: 16%).

Conclusion: Edema affects approximately 60% of patients with nephrotic-range albuminuria and hypoalbuminemia, associated with increased risk of venous thromboembolism, faster kidney failure progression, and higher one-year all-cause mortality, highlighting its prognostic information in nephrotic syndrome.

Background: IgA nephropathy is the most common primary kidney disease in the world and has a highly variable clinical presentation. While studies have indicated a link between glomerular disease and infections, large-scale studies on IgA nephropathy are missing.

Methods: In our study, IgA nephropathy was defined as having a kidney biopsy record 1997-2011 in Sweden. Each IgA nephropathy patient was matched with five reference individuals based on age, sex, calendar year, and county of residence. We excluded individuals with earlier organ transplants, HIV, immunodeficiency, or end-stage kidney disease. Linear and Cox regressions, adjusted for age, sex, education and diabetes, were performed to analyze total infections and antimicrobial treatments in both patients and reference individuals. Sibling analyses were also performed.

Results: The linear regression analysis revealed a significant association between IgA nephropathy and the overall frequency of infections compared to the general population (β=0.44; 95%CI: 0.35-0.53) and siblings (β=0.36; 95%CI:0.23-0.49). Similarly, antimicrobial prescriptions, especially antibiotics, were more common in IgA nephropathy compared to the general population and to siblings. Cox regression showed an elevated risk of any infection (adjusted hazard ratio (HR)=2.00; 95%CI 1.84-2.18) and sepsis (aHR=3.18; 95%CI 2.17-4.65) corresponding to one extra case of sepsis per 63 patients followed for 10 years. The strongest associations were seen for urinary tract infections; ear, nose, and throat infections; musculoskeletal and gastrointestinal infections.

Conclusion: Conclusively, our study demonstrates an increased prevalence of infections and antibiotic prescriptions in IgA nephropathy patients. The increased risk of sepsis warrants clinical awareness and prevention.

Rationale & Objective: Clinical practice guidelines recommend lower (35.0°C-35.5°C) instead of standard dialysate temperature (36.5°C-37.0°C) to mitigate the risk of intradialytic hypotension. However, many studies have been available since the recommendations were published. Hence, the current study aims to provide an updated meta-analysis of clinical outcomes with cold versus standard dialysate.

Study design: Systematic review and meta-analysis of eligible articles indexed in PubMed, Cochrane, Web of Science, and Scopus.

Participants: Hemodialysis patients Exposure: Cooled versus standard dialysate.

Outcome: Intradialytic hypotension, mean arterial pressure, thermal-related discomfort, and body temperature.

Analytical approach: The random effects model was used for all outcomes due to high heterogeneity (I2: interdialytic hypotension=60%, mean arterial pressure=72%, symptoms of discomfort =41%, and decrease in body temperature=87%). The "leave-one-out" approach was used for sensitivity analysis, and the Cochrane risk-of-bias tool was used to evaluate study quality.

Results: Pooled data from 31 studies indicate that cooled dialysis may be associated with a lower risk of intradialytic hypotension [RR 0.67 (95%CI 0.48-0.93), p=0.02] and higher mean arterial pressure [MD 7.18 (95%CI 3.79-10.58), p<0.01] compared to standard temperature dialysis. However, cooled dialysis was associated with a higher risk of discomfort [RR 1.55 (95% CI 1.25-1.93], p<0.01] and a decrease in body temperature [MD -0.29 (95%CI -0.52--0.05), p=0.02]. Only five studies had a low risk of bias.

Limitations: Most included studies were from over a decade ago, had a small participant size, and did not report other critical long-term outcomes such as mortality, cardiovascular events, treatment discontinuation, or hospitalization rate.

Registration: Registered with ID CRD42024589307 at PROSPERO Conclusions: Using cooled dialysate might be a simple approach to reduce interdialytic hypotension risk and increase mean arterial pressure, albeit at the cost of patient discomfort. The limitations associated with the quality of included studies underscore the need for high-quality, multicenter studies with large/diverse study populations.

Introduction: Maintaining renin-angiotensin-aldosterone system inhibition (RAASi) in advanced chronic kidney disease (CKD) to delay CKD progression is still controversial. This is due to potential side effects associated with RAASi, such as a decline in glomerular filtration rate (GFR) and hyperkalemia. This study aims to examine the effect of RAASi on progression of advanced CKD to kidney failure (eGFR <15 ml/min/1.73 m2, CKD stage 5) in a real-life outpatient cohort.

Methods: This single-center retrospective observational study presents data from 954 individuals with advanced CKD (estimated glomerular filtration rate [eGFR] 15-30 ml/min/1.73 m2), comparing 806 RAASi with 511 control intervals over a median follow-up period of 19 months. The endpoint was defined as time to manifestation of kidney failure. Univariate and multivariate time-to-event analysis were performed to assess effects of RAASi on endpoint probabilities.

Results: Univariate time-to-event analysis did not show a significant difference in the median time to kidney failure between RAASi and control intervals (7.6 vs. 7.0 years, p=0.74). Covariate-adjusted multivariate regression models also demonstrated no association between RAASi treatment and progression to kidney failure in patients with advanced CKD (hazard ratio 0.92 [95% CI: 0.67 - 1.23], p=0.63).

Conclusion: RAASi has no significant impact on the time to kidney failure in patients with advanced CKD. Hence, this study supports maintenance of RAASi in advanced CKD, if used for extrarenal indications such as cardiovascular protection.

Introduction: Home dialysis modalities offer several clinical and economic benefits compared to facility-based dialysis treatment in patients with kidney failure. Studies have shown that sex and socioeconomic status (SES) disparities exist in access to dialysis and transplantation in patients with kidney failure, but whether similar disparities occur in the access to home dialysis after kidney transplant failure is unknown.

Methods: Using data from ANZDATA registry, patients who commenced dialysis after kidney transplant failure in Australia were included (2000-2020). The associations between sex and uptake of peritoneal (PD) and home haemodialysis (HHD) at 12-months after kidney transplant failure were examined using adjusted logistic regression, with interactive effect between sex and SES evaluated.

Results: Of 3521 patients who experienced first kidney transplant failure, 1352 (38%) were females. At 12-months following transplant failure, 483(14%) were maintained on PD and 425 (12%) on HHD. Compared to females, males were less likely to select PD at 12-months after transplant failure, with an adjusted OR (95%CI) of 0.55 (0.44-0.68). The adjusted OR (95%CI) for the uptake of HHD at 12-months in males was 1.66 (1.29-2.12). There were significant interactions between sex and SES for the 12-month uptake of PD and HHD, such that for patients from socioeconomically disadvantaged areas, the respective adjusted ORs for the uptake of PD and HHD in male patients were 0.61 (0.45-0.84) and 2.25 (1.51-3.51) compared to female patients.

Conclusion: Males who lost their kidney allografts were more likely to choose HHD over PD compared to female patients. This sex disparity was more pronounced in individuals from socioeconomically disadvantaged areas.

Background: Electrolyte disorders are common in cancer patients and have significant impacts on treatment outcomes and quality of life. The frequency, severity, complexity and etiology of fluid and electrolyte disorders is different among cancer patients when compared to the general population.

Summary: This review describes the key electrolyte imbalances and pathogenesis, including sodium disorders, potassium disorders, and abnormalities in magnesium, calcium, and phosphorus levels, within the context of cancer therapies. Cancer specific therapies reviewed surgical and radiologic therapies, cellular therapies, use of checkpoint inhibitors and traditional cytotoxic chemotherapy that can result in specific patterns of electrolyte derangements.

Key message: The objective of this article is to highlight clinical presentations and to discuss management of some cancer specific electrolyte disturbances. This article underscores the importance of regular electrolyte monitoring and timely intervention in managing cancer patients.

Introduction: Different uremic solutes have varying degrees of clearances owing to different chemical properties and the pathological and physiological changes in the kidneys and peritoneum.

Methods: The 5-year time profiles of renal, peritoneal, and total clearances of creatinine, urea nitrogen (UN), uric acid (UA), trimethylamine N-oxide (TMAO), phosphate, beta-2-microglobulin(β2-MG), interleukin-6 (IL-6), indoxyl sulfate (IS), and p-cresol sulfate (PCS) were investigated in 64 peritoneal dialysis (PD) patients. The patients were divided into an early start and a late start group according to baseline estimated glomerular filtration rate to investigate the effect of dialysis initiation timing on uremic solutes clearances. Patients were also divided into incremental peritoneal dialysis (IPD) and full-dose PD groups to investigate the impact of PD strategy on uremic solutes clearances.

Results: Peritoneal clearances of creatinine, UN, UA, and phosphate increased over time, while the peritoneal clearance of IL-6 showed a downward trend. The peritoneal clearances of TMAO, β2-MG, IS, and PCS did not change significantly. Patients in early start group showed a lower level of variation and a higher average of renal clearances. IPD patients had a higher level of total clearances of uremic solutes than full-dose PD patients in the first three years after PD initiation.

Conclusion: In a long-term follow-up period, the peritoneal clearance of water-soluble small solutes increased over time, but that of protein-bound toxins and middle molecules did not. Initiating PD when residual kidney function remains at a relatively high level and performing IPD may better improve the efficiency of PD and help preserve the renal clearances of uremic solutes.

Introduction: Sustained 30% reductions of intact parathyroid hormone (iPTH) with ERC are associated with slower decline in estimated glomerular filtration rate (eGFR) in ND-CKD patients with SHPT. Such iPTH reductions usually require elevation of serum total 25-hydroxyvitamin D (25D) to ≥50 ng/mL, but achieving these reductions can be limited by the ERC dose ceiling (60 μg/day), raising the question of whether adjunctive (adj) AVD might be appropriate to further reduce iPTH.

Methods: This randomized controlled trial (RCT) examined whether adj AVD could safely increase iPTH reductions achieved with ERC and further reduce the rate of eGFR decline in 78 ND-CKD adults treated with ERC for 38 weeks. Participants had mean age of 66 years, body mass index of 35 kg/m2, 41% were female, 63% White, 36% Black, 19% Hispanic. At ERC initiation, participants had plasma iPTH 85-<500 pg/mL, eGFR 15-<60 mL/min/1.73 m2, serum 25D 10-<30 ng/mL, corrected serum calcium (Ca) 8.4-<9.8 mg/dL, serum phosphorus (P) 2.0-<5.0 mg/dL, and absence of macroalbuminuria (>300 mg/g creatinine). At baseline (BL; week 38), participants had plasma iPTH >70 pg/mL and serum Ca <9.8 mg/dL and were randomized 3:1:1:1 to daily ERC (60 μg) for 14 additional weeks with (n=40) or without (n=38) adj daily oral calcitriol (0.25 μg), doxercalciferol (0.5 μg) or paricalcitol (1.0 μg). Measurements of eGFR, iPTH, 25D, Ca, P and fibroblast growth factor 23 (FGF23) were obtained at BL and through end of treatment (EOT).

Results: No significant intergroup differences were observed at BL. Mean 25D at BL was 65 ng/mL and rose 14 ng/mL by EOT in both groups (p<0.001). Mean BL iPTH was 137 pg/mL and fell by a further 35.4% (p<0.001) with adj AVD therapy versus 2.2% without. Mean Ca, P and FGF23 increased with adj AVD by 0.40 mg/dL (p<0.001), 0.27 mg/dL (p<0.01) and 49.1 pg/mL (155%; p<0.001), respectively, but remained unchanged with ERC alone. Mean BL eGFR was 25.4 mL/min/1.73m2 and fell by 11.8% (p<0.05) with adj AVD versus 3.0% without.

Conclusion: Adj AVD at these doses enabled 35% more iPTH reduction in ND-CKD patients with mild to moderate SHPT on long-term ERC treatment but increased mean serum Ca and P by 0.40 and 0.27 mg/dL, respectively, FGF23 by more than 2-fold and eGFR decline by 4-fold, suggesting that adding AVD to ERC has untoward effects that override the nephrosparing impact of iPTH reductions with ERC treatment alone. Corroboration is warranted with a larger, longer RCT.

Introduction: Recent experimental studies have reported that fibroblast growth factor 23 (FGF23) inhibits erythropoiesis by suppressing erythropoietin (EPO) production and downregulating the EPO receptor. Conversely, either endogenous or exogenous EPO has been shown to stimulate FGF23 production. However, little is known about the relationships between FGF23, erythropoiesis-stimulating agent (ESA) treatment, ESA resistance, and endogenous EPO in hemodialysis patients.

Methods: We analyzed cross-sectional data from a cohort of 654 maintenance hemodialysis patients. We examined the associations of intact or C-terminal FGF23 with ESA treatment, ESA resistance index (ERI), hemoglobin, C-reactive protein, and endogenous EPO levels using linear regression models. EPO was measured only in patients not receiving ESAs.

Results: A total of 458 patients (70%) were treated with ESAs. The median EPO concentration in non-ESA users was 7.8 (interquartile range, 5.3-14.4) mIU/mL. The median levels of intact and C-terminal FGF23 were 1,598 (interquartile range, 548-4,586) pg/mL and 38.7 (interquartile range, 14.0-127.6) pmol/L, respectively, in non-ESA users and 1,955 (interquartile range, 573-5,264) pg/mL and 41.4 (interquartile range, 13.9-116.8) pmol/L, respectively, in ESA users. After adjustment for potential confounders, higher ESA dose was associated with higher FGF23 levels measured by both intact and C-terminal assays. Higher C-terminal FGF23 was also associated with higher ERI, lower hemoglobin, and higher endogenous EPO, but no such associations were observed for intact FGF23 levels.

Conclusions: Both intact and C-terminal FGF23 showed similar associations with ESA dose, but they showed different patterns of association with other parameters related to anemia. Further research is needed to elucidate the mechanisms underlying these different associations.

Background Kidney transplant is a treatment of choice for end-stage kidney disease, with longer survival and better quality of life post-transplant. However, long-term immunosuppression comes with an increased risk of cancer and infection. Cancer is one of the leading causes of death after kidney transplant. While novel cancer therapies become available, transplant recipients are usually excluded from clinical trials Summary In this review, we summarize the updated knowledge on immunosuppression management in kidney transplant recipients treated with immune checkpoint inhibitors, bispecific T cell engager (BiTE) therapy, and chimeric antigen receptor (CAR) T cell therapies. Key Messages Transplant nephrologists should be empowered to participate in the decision making of cancer treatment together with patients, care partners and oncologist, by managing immunosuppression.