American Journal of Nephrology最新文献

Introduction: Dry weight management in dialysis patients is crucial but often subjective, primarily based on symptoms. Due to continuous fluid removal in peritoneal dialysis (PD) and intermittent ultrafiltration in hemodialysis (HD), symptom-based assessments may be biased, leading to varying results. Surprisingly, no direct comparison of dry weight changes between PD and HD has been conducted. This study aimed to evaluate the impact of transitioning from PD to HD on body weight and related clinical parameters.

Methods: This retrospective cohort study included 127 stable PD patients who transitioned to HD. Changes in body weight, echocardiographic parameters, albumin, and hemoglobin levels were analyzed over a 1-year period post-transition.

Results: The mean patient age was 57.1 ± 15.5 years, with an average PD vintage of 5.8 ± 4.9 years. Most patients had hypertension. After transitioning to HD, body weight decreased significantly, with a reduction of -2.8 kg at 1 month, -5.3 kg at 3 months, and -7.5 kg 1 year post-transition. Echocardiographic parameters showed no significant changes. However, serum albumin and hemoglobin levels increased slightly but significantly after the transition, and the number of antihypertensive medications was also reduced.

Conclusion: The transition from PD to HD results in significant reductions in body weight. These findings underscore the often-overlooked issue of fluid overload in PD patients and its potential impact on patient outcomes.

Introduction: We intended to compare the predictive value for all-cause and cardiovascular deaths between estimated glomerular filtration rate (eGFR) derived from the European Kidney Function Consortium (EKFC) cystatin C-based formula, the EKFC creatinine-based formula, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C- or creatinine-based formulas.

Methods: Overall, 4,132 participants from the National Health and Nutrition Examination Survey between 1999 and 2002 were included, and death information was obtained through the National Death Index. To compare predictive accuracy between EKFC eGFRcys (EKFC cystatin C-based formula), CKD-EPI eGFRcys (CKD-EPI cystatin C-based formula), EKFC eGFRcr (EKFC creatinine-based formula), and CKD-EPI eGFRcr (CKD-EPI creatinine-based formula), we conducted time-dependent receiver operator characteristic (ROC) curves and reclassification analysis.

Results: During a median follow-up of 17.4 years, a total of 1,987 all-cause and 530 cardiovascular deaths were confirmed. Restricted cubic splines analyses showed that reduced EKFC eGFRcys was linearly related to higher risks of all-cause and cardiovascular deaths (p for nonlinearity > 0.05). Time-dependent ROC curves suggested that EKFC eGFRcys exhibited higher predictive ability than CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr at 5-year and 10-year follow-ups. For 10-year all-cause deaths, EKFC eGFRcys yielded significant improvement over CKD-EPI eGFRcr (integrated discrimination improvement [IDI], 9.4%; net reclassification improvement [NRI], 39.7%). Similar improvement was observed in 10-year cardiovascular deaths when comparing EKFC eGFRcys to CKD-EPI eGFRcr (IDI, 6.7%; NRI, 45.1%).

Conclusion: The EKFC eGFRcys outperformed CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr in predicting all-cause and cardiovascular deaths, providing the possibility to utilize EKFC eGFRcys in the stratification of death risk among the general US population.

Introduction: Angiotensin II may reduce muscle ischemia during intermittent hemodialysis (IHD) and thereby decrease the incidence and/or intensity of intradialytic muscle cramps. We aimed to test whether angiotensin II infusion during IHD is safe, feasible, and effective in the attenuation of muscle cramps.

Methods: We performed a pilot, single-blinded, randomized crossover trial of patients receiving IHD who frequently experience intradialytic muscle cramps. Patients were randomly allocated to receive either intravenous angiotensin II or placebo for the duration of their first dialysis session of the week. They crossed over to the alternate arm each week for 4 weeks. The primary outcome was safety. Secondary outcomes included cramp-related symptoms, hemodynamic parameters, dialysis prescription alterations, and biomarkers.

Results: We studied 24 sessions in 6 patients. Intradialytic hypertension (systolic blood pressure >180 mm Hg) occurred more often with angiotensin II than with placebo (4/12 sessions, 33% vs. 2/12 sessions, 17% sessions, p = 0.64). There were no other adverse events. Compared with placebo, muscle cramps were less frequent (4/12 sessions, 33% vs. 11/12 sessions, 92% sessions, p = 0.009) and of lower intensity with angiotensin II (median Brief Pain Inventory score 1.4 vs. 5.3; p < 0.001; maximal Brief Pain Inventory score 1.2 vs. 6.0; p < 0.001). Fluid bolus administration for cramps was less common during angiotensin II infusion than placebo (0/12 sessions, 0% vs. 5/12 sessions, 42% sessions, p = 0.037).

Conclusion: Angiotensin II increased blood pressure and heart rate but not cardiac output or levels of troponin, creatine kinase, or renin. Angiotensin II infusion during IHD appears safe and effective at reducing intradialytic muscle cramps. These observations justify further investigation in larger controlled studies.

Introduction: Thrombotic microangiopathies (TMAs) represent distinct pathological and clinical entities with known chronicity and recurrence. Kidney biopsy is the gold standard to diagnose TMA in patients with renal manifestations, but the prognostic significance of acute or chronic phase of the disease has not been well studied. We examined the clinical characteristics, management, and predictors of acute versus chronic TMA among native and transplants.

Methods: Observational, cross-sectional study of a 22-year period at Johns Hopkins Hospital. Prevalence of acute versus chronic TMA was based on specific histology identified on native and allograft kidney biopsies. Predictors of acute and chronic TMA were assessed using simple linear regression and odds ratios.

Results: Among 127 patients, 29 (23%) had chronic TMA and 98 (77%) had acute TMA, with 60% female and 43 ± 18 years of age. Chronic TMA was significantly associated with a history of lupus or hemolytic uremic syndrome (HUS) and the use of clopidogrel or mammalian target of rapamycin inhibitors (mTORi). Specifically, chronic TMA was significantly associated with use of mTORi in native kidneys. The odds of chronic TMA compared to acute TMA were lower for each race (Caucasians, 76%; blacks, 38%; Hispanics and Asians, 22%).

Conclusions: A kidney biopsy may not necessarily be needed to determine the presence of chronic TMA since certain predictors, as those demonstrated by our study (use of mTORi and history of lupus or HUS), independently predicted higher odds of developing chronic TMA and its sequelae conditions.

Introduction: The Kidney Disease: Improving Global Outcomes guidelines recognize the importance of causes of chronic kidney disease (CKD), glomerular filtration rate, and albuminuria as predictors of kidney outcome and prognosis. However, compared with biopsy-proven causes, there has been limited research regarding the relationship between clinically diagnosed causes of CKD and patient prognosis.

Methods: We examined 3,119 patients with non-dialysis-dependent CKD who participated in the Fukuoka Kidney disease Registry Study, a multicenter prospective cohort study. Patients were divided into six groups: IgA nephropathy, chronic glomerulonephritis (non-biopsy-proven), diabetic nephropathy, hypertensive nephrosclerosis, chronic interstitial nephritis, and polycystic kidney disease. The primary outcomes included a composite kidney outcome, defined as a 1.5-fold increase in serum creatinine and/or the development of end-stage kidney disease, and all-cause mortality. The risks of these outcomes were estimated using a Fine-Gray proportional subdistribution hazards model. Patients with IgA nephropathy, the most prevalent primary glomerulonephritis, served as the reference group.

Results: During the median follow-up period of 5 years, 1,221 patients developed the composite kidney outcome, and 346 patients died. Compared with IgA nephropathy, the multivariable-adjusted subdistribution hazard ratios (sHRs) for the composite kidney outcome were significantly higher in diabetic nephropathy (sHR 1.45) and polycystic kidney disease (sHR 2.07) groups, whereas the chronic interstitial nephritis group had a significantly lower risk (sHR 0.71). The risk of all-cause mortality was significantly higher in the hypertensive nephrosclerosis group (sHR 1.90).

Conclusion: The causes of CKD were associated with risks of the composite kidney outcome and all-cause mortality, highlighting their clinical relevance in predicting prognosis. These findings suggest that different causes of CKD have distinct impacts on patient outcomes, emphasizing the importance of tailoring management strategies according to the underlying causes.

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used over the past decade for treatment of several cancer types. Despite the excellent cancer response they provide, their use has been associated with serious immune-related adverse events affecting multiple systems including the kidney. Currently, limited data are available to guide treatment of acute kidney injury secondary to ICI use (ICI-AKI) due to tubulointerstitial nephritis or glomerulonephritis. Another huge obstacle is the safety of resuming ICI following an episode of ICI-AKI.

Summary: Acute tubulointerstitial nephritis (ATIN) is the most common pathology associated with ICI-AKI, followed by other less common forms of glomerulonephritis. Management of this disorder is very challenging. Corticosteroids therapy remains the mainstay treatment for patients with ICI-ATIN. Use of other immunosuppressants for ICI-ATIN and recurrent ICI-ATIN has been also described in the literature. In patients with ICI-related glomerulonephritis, the use of rituximab is the more common approach reported in the literature. Regarding the safety to resume ICI following an episode of ICI-AKI, this decision should be made following a multidisciplinary approach on a case-by-case basis.

Key messages: Limited evidence is available to guide management in patients with ICI-AKI. More prospective studies are needed in the future to better guide treatment of cancer patients with ICI-AKI.

Introduction: Although both patients with kidney failure (KF) receiving hemodialysis (HD) and kidney transplantation (KT) recipients (KTRs) have a high risk of bladder cancer, how this risk changes in the transition from dialysis to KT is unknown. In this study, we aimed to investigate the risk of bladder cancer in KTRs and patients on HD.

Methods: This was a nationwide longitudinal cohort study of 66,547 participants from the National Health Insurance Service cohort who started HD for patients with KF or who received KT from 2002 to 2020. The primary outcome was the diagnosis of bladder cancer, which was defined as the composite of diagnostic codes and either hospitalization or ≥2 outpatient visits for bladder cancer.

Results: During mean follow-ups of 4.2 and 7.9 years in the HD and KT groups, respectively, the incidence rates of bladder cancer were 1.1/1,000 and 0.3/1,000 person-years, respectively. In the time-dependent multivariable Cox models, compared to patients on HD, the adjusted hazard ratio (aHR) for bladder cancer among KTRs was 0.36 (95% confidence interval [CI], 0.21-0.60; p < 0.001). Among men, this aHR was 0.29 (95% CI, 0.15-0.55; p < 0.001); however, no statistically significant association between the kidney replacement therapy modality and the risk of bladder cancer was observed among women. Landmark analysis performed to avoid immortal time bias by redefining time zero as a specific landmark time (2 and 5 years after HD initiation or KT) revealed similar results.

Conclusion: The risk of bladder cancer was significantly lower among KTRs than that among patients receiving HD, particularly among men.

Introduction: Although studies have suggested that metabolic risk profiles are prognostic factors in kidney transplantation recipients (KTRs), the prognostic value of fatty liver, a known surrogate of metabolic risk, in KTRs remains to be elucidated. The objective of this study was to investigate the association between noninvasive liver biomarkers used to assess hepatic steatotic and fibrotic burdens and graft outcomes in KTRs.

Methods: A total of 3,092 patients who underwent deceased or living donor kidney transplantation (KT) between January 2000 and December 2022 were enrolled. Postoperative hepatic fibrotic burdens of KTRs were assessed using the fibrosis-4 (FIB-4) score and the non-alcoholic fatty liver disease fibrosis score (NFS). The primary outcome was a composite of 50% estimated glomerular filtration rate (eGFR) decline and graft failure. Secondary outcomes included individual outcomes of 50% eGFR decline, graft failure, and acute rejection.

Results: For the primary outcome, during a mean follow-up of 6.0 years, the composite outcome occurred in 519 (16.8%) participants. When stratified into three groups according to FIB-4 score categories, the highest score group (FIB-4 ≥2.67) had a 2.05-fold (95% confidence interval [CI], 1.44-2.91; p < 0.001) higher risk of the composite outcome compared to the lowest score group (FIB-4 <1.30). Furthermore, the highest score group showed higher risk of the secondary outcomes, with hazard ratios (95% CI) of 1.75 (1.16-2.66), 1.62 (1.06-2.46), and 2.23 (1.43-3.46) for 50% eGFR decline, acute rejection, and graft failure, respectively. Similar findings were observed for NFS.

Conclusions: Higher hepatic fibrotic burdens were associated with unfavorable graft outcomes in KTRs.

Introduction: Chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) are more prevalent in the elderly. There is a lack of large animal models that allow the study of the impact of age on CKD and HFpEF in a translational fashion. This manuscript reports the first large preclinical model of CKD-HFpEF and metabolic derangements in naturally aged swine.

Methods: CKD-HFpEF was induced in naturally aged (6-9 years old) and young (3 months old) pigs, followed for 14 weeks, and compared to normal young and old controls (n = 5/group). Renal and cardiac hemodynamics were quantified in vivo by multidetector-CT, echocardiography, and pressure-volume relationship studies. Renal and cardiac microvascular (MV) architecture (3D-micro-CT) and morphometric analysis (staining) were investigated ex vivo.

Results: Both young and old pigs developed CKD-HFpEF, but the renal, cardiac, and metabolic phenotype was accentuated in aging animals. Aging and CKD-HFpEF influenced fasting insulin levels and insulin resistance, glomerular filtration rate, cortical MV density, glomerulosclerosis, perivascular fibrosis, and tubular injury. Tubule-interstitial fibrosis and peritubular capillary density were influenced by aging, CKD-HFpEF, and their interaction (2-way ANOVA). Similarly, cardiac MV density, perivascular fibrosis, and myocardial remodeling were influenced by aging and CKD-HFpEF, and E/A by their interaction. Notably, renal and cardiac MV density correlated with renal and cardiac functional and structural changes.

Conclusion: Our study establishes the first large animal model of aging CKD-HFpEF, allowing the investigation of age as a biological variable in cardiorenal and metabolic diseases. This new platform could foster new age-related research toward developing therapeutic interventions in CKD-HFpEF.

Introduction: The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) developed new race-free eGFR equations and recommended using these new equations in 2021. However, clinical implication of these new equations is not determined in Korean adults. Thus, this study aimed to evaluate performances of these new race-free eGFR equations in predicting complications in Korean chronic kidney disease (CKD) patients.

Methods: This study analyzed 1,727 participants from the KNOW-CKD cohort. We selected anemia, hyperkalemia, acidosis, hyperphosphatemia, and hyperparathyroidism as five complications of CKD. We determined cross-sectional associations between complications and four eGFR equations. These eGFRs were calculated from 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (2009 eGFRCr), 2012 CKD-EPI Creatinine-Cystatin C equation (2012 eGFRCrCys), 2021 CKD-EPI Creatinine equation (2021 eGFRCr), and 2021 CKD-EPI Creatinine-Cystatin C equation (2021 eGFRCrCys).

Results: All associations between complications as continuous variables and eGFR by four equations were similar. All associations between complications as dichotomous variable and eGFR values form four equations were similar. For example, C-statistics (95% confidence interval) of the logistic model for anemia and eGFRs were 0.826 (0.806-0.845), 0.827 (0.806-0.846), 0.838 (0.819-0.857), and 0.839 (0.820-0.858) for 2009 eGFRCr, 2012 eGFRCrCys, 2021 eGFRCr, and 2021 eGFRCrCys, respectively. In addition, cross-validated areas under the curve for ROC analysis after predictive modeling for all complications were not significant different according to different eGFR equations.

Conclusion: New race-free eGFR equations showed similar performances to existing equations for predicting complications in Korean patients with CKD.