BACKGROUND: The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland.
METHODS: This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1-G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant.
RESULTS: Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084-0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years.
CONCLUSIONS: The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.

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UNASSIGNED: Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship.
UNASSIGNED: Retrospective cohort study.
UNASSIGNED: 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to 2013.
UNASSIGNED: AKI, AKI severity, and age.
UNASSIGNED: KFRT and death.
UNASSIGNED: The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death.
UNASSIGNED: Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity.
UNASSIGNED: Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity.
UNASSIGNED: In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.
Older adults are at risk of acute kidney injury (AKI) and subsequent nonrecovery from AKI, resulting in long-term dialysis. Hospitalized patients have often been used in the past to study AKI. This could lead to biased conclusions when inferring from sicker populations. That is why we created a national cohort of 24,133 Veterans at least 65 years old with incident chronic kidney disease (CKD) stage 4 to examine the relationship between AKI and age and subsequent kidney failure with replacement therapy (KFRT). The data have showed that AKI and younger age are substantial risk factors for incident KFRT. As for older age, it appears to be protective against KFRT but not death. This is likely explained by the high frequency of deaths observed in our cohort.

OBJECTIVE: High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT).
METHODS: We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1-199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT.
RESULTS: During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02-2.87) and 2.55 (95 % CI, 1.07-6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis.
CONCLUSIONS: CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression.

BACKGROUND: The Columbia classification identified five histological variants of focal segmental glomerulosclerosis (FSGS). The prognostic significance of these variants remains controversial.
OBJECTIVE: To evaluate the relative frequency, clinicopathologic characteristics, and medium-term outcomes of FSGS variants at a single center in Pakistan.
METHODS: This retrospective study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan on all consecutive adults (≥ 16 years) with biopsy-proven primary FSGS from January 1995 to December 2017. Studied subjects were treated with steroids as a first-line therapy. The response rates, doubling of serum creatinine, and kidney failure (KF) with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis, and Chi-square tests as appropriate. Data were analyzed by SPSS version 22.0. P-value ≤ 0.05 was considered significant.
RESULTS: A total of 401 patients were diagnosed with primary FSGS during the study period. Among these, 352 (87.7%) had a designated histological variant. The not otherwise specified (NOS) variant was the commonest, being found in 185 (53.9%) patients, followed by the tip variant in 100 (29.1%) patients. Collapsing (COL), cellular (CEL), and perihilar (PHI) variants were seen in 58 (16.9%), 6 (1.5%), and 3 (0.7%) patients, respectively. CEL and PHI variants were excluded from further analysis due to small patient numbers. The mean follow-up period was 36.5 ± 29.2 months. Regarding response rates of variants, patients with TIP lesions achieved remission more frequently (59.5%) than patients with NOS (41.8%) and COL (24.52%) variants (P < 0.001). The hazard ratio of complete response among patients with the COL variant was 0.163 [95% confidence interval (CI): 0.039-0.67] as compared to patients with NOS. The TIP variant showed a hazard ratio of 2.5 (95%CI: 1.61-3.89) for complete remission compared to the NOS variant. Overall, progressive KF was observed more frequently in patients with the COL variant, 43.4% (P < 0.001). Among these, 24.53% of patients required kidney replacement therapy (P < 0.001). The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57 (95%CI: 1.87-113.49) as compared to patients with the TIP variant.
CONCLUSIONS: In conclusion, histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

BACKGROUND: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients.
METHODS: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT).
RESULTS: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR.
CONCLUSIONS: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.

Heart-kidney crosstalk is recognized as the cardiorenal syndrome. We examined the association of cardiac function and structure with the risk of kidney failure with replacement therapy (KFRT) in a chronic kidney disease (CKD) population.
Prospective observational cohort study.
3,027 participants from the Chronic Renal Insufficiency Cohort Study.
Five preselected variables that assess different aspects of cardiac structure and function: left ventricular mass index (LVMI), LV volume, left atrial (LA) area, peak tricuspid regurgitation (TR) velocity, and left ventricular ejection fraction (EF) as assessed by echocardiography.
Incident KFRT (primary outcome), and annual estimated glomerular filtration rate (eGFR) slope (secondary outcome).
Multivariable Cox models and mixed-effects models.
The mean age of the participants was 59±11 SD years, 54% were men, and mean eGFR was 43±17mL/min/1.73m2. Between 2003 and 2018 (median follow-up, 9.9 years), 883 participants developed KFRT. Higher LVMI, LV volume, LA area, peak TR velocity, and lower EF were each statistically significantly associated with an increased risk of KFRT, with corresponding HRs for the highest versus lowest quartiles (lowest vs highest for EF) of 1.70 (95% CI, 1.27-2.26), 1.50 (95% CI, 1.19-1.90), 1.43 (95% CI, 1.11-1.84), 1.45 (95% CI, 1.06-1.96), and 1.26 (95% CI, 1.03-1.56), respectively. For the secondary outcome, participants in the highest versus lowest quartiles (lowest vs highest for EF) had a statistically significantly faster eGFR decline, except for LA area (ΔeGFR slope per year, -0.57 [95% CI, -0.68 to-0.46] mL/min/1.73m2 for LVMI, -0.25 [95% CI, -0.35 to-0.15] mL/min/1.73m2 for LV volume, -0.01 [95% CI, -0.12 to-0.01] mL/min/1.73m2 for LA area, -0.42 [95% CI, -0.56 to-0.28] mL/min/1.73m2 for peak TR velocity, and -0.11 [95% CI, -0.20 to-0.01] mL/min/1.73m2 for EF, respectively).
The possibility of residual confounding.
Multiple aspects of cardiac structure and function were statistically significantly associated with the risk of KFRT. These findings suggest that cardiac abnormalities and incidence of KFRT are potentially on the same causal pathway related to the interaction between hypertension, heart failure, and coronary artery diseases.
Heart disease and kidney disease are known to interact with each other. In this study, we examined whether cardiac abnormalities, as assessed by echocardiography, were linked to the subsequent progression of kidney disease among people living with chronic kidney disease (CKD). We found that people with abnormalities in heart structure and function had a greater risk of progression to advanced CKD that required kidney replacement therapy and had a faster rate of decline in kidney function. Our study indicates the potential role of abnormal heart structure and function in the progression of kidney disease among people living with CKD.

In patients with kidney failure with replacement therapy (KFRT), optimizing anemia management in these patients is a challenging problem because of the complexities of the underlying diseases and heterogeneous responses to erythropoiesis-stimulating agents (ESAs). Therefore, we propose a ESA dose recommendation model based on sequential awareness neural networks. Data from 466 KFRT patients (12,907 dialysis sessions) in seven tertiary-care general hospitals were included in the experiment. First, a Hb prediction model was developed to simulate longitudinal heterogeneous ESA and Hb interactions. Based on the prediction model as a prospective study simulator, we built an ESA dose recommendation model to predict the required amount of ESA dose to reach a target hemoglobin level after 30 days. Each model\'s performance was evaluated in the mean absolute error (MAE). The MAEs presenting the best results of the prediction and recommendation model were 0.59 (95% confidence interval: 0.56-0.62) g/dL and 43.2 μg (ESAs dose), respectively. Compared to the results in the real-world clinical data, the recommendation model achieved a reduction of ESA dose (Algorithm: 140 vs. Human: 150 μg/month, P < 0.001), a more stable monthly Hb difference (Algorithm: 0.6 vs. Human: 0.8 g/dL, P < 0.001), and an improved target Hb success rate (Algorithm: 79.5% vs. Human: 62.9% for previous month\'s Hb < 10.0 g/dL; Algorithm: 95.7% vs. Human:73.0% for previous month\'s Hb 10.0-12.0 g/dL). We developed an ESA dose recommendation model for optimizing anemia management in patients with KFRT and showed its potential effectiveness in a simulated prospective study.

OBJECTIVE: High anion gap acidosis frequently develops in patients with advanced chronic kidney disease (CKD) and might be involved in kidney injury. Its impact on kidney outcomes, however, has not been well studied. We sought to examine the association between time-updated anion gap and the risk of kidney failure with replacement therapy (KFRT) among patients with advanced CKD.
METHODS: Retrospective cohort study.
METHODS: 1,168 patients with CKD glomerular filtration rate categories 3b-5 (G3b-G5) who had available data on anion gap.
METHODS: High time-updated anion gap defined as values ≥ 9.2 (top 25th percentile).
RESULTS: KFRT and death.
UNASSIGNED: Marginal structural models were fit to characterize the association between anion gap and study outcomes while accounting for potential time-dependent confounding.
RESULTS: The mean baseline estimated glomerular filtration rate (eGFR) of the study participants was 28 mL/min/1.73 m2. Over a median follow-up period of 3.1 years, 317 patients progressed to KFRT (7.5 per 100 patient-years), and 146 died (3.5 per 100 patient-years). In the marginal structural models, a high anion gap was associated with a higher rate of KFRT (HR, 3.04 [95% CI, 1.94-4.75]; P < 0.001). This association was stronger in patients with a baseline eGFR of <30 mL/min/1.73 m2 (P for interaction = 0.05). High anion gap was also associated with a higher mortality rate (HR, 5.56 [95% CI, 2.95-10.5]; P < 0.001). Sensitivity analyses with different definitions of high anion gap showed similar results.
CONCLUSIONS: Observational study design and selection bias due clinical indications for measuring anion gap.
CONCLUSIONS: Among patients with advanced CKD, high anion gap was associated with an increased risk of progression to KFRT and death.

Over the past few decades, there has been increasing recognition of kidney disease in children with non-kidney solid organ transplantation. The risk of kidney disease in children undergoing heart or liver transplantation is higher than the general population as the underlying disease and its associated management may directly impair kidney function. Both heart and liver failures contribute to hypoperfusion and kidney ischemia before patients reach the point of transplant. The transplant surgery itself can often be complicated by acute kidney injury (AKI), which may be further exacerbated by a complicated postoperative course. In the short- and long-term post-transplant period, these children are at risk of acute illness, exposed to nephrotoxic medications, and susceptible to rare but severe infections and immunologic insults that may contribute to AKI and chronic kidney disease (CKD). In some, CKD can progress to kidney failure with replacement therapy (KFRT). CKD and KFRT are associated with increased morbidity and mortality in this patient population. Therefore, it is critical to monitor for and recognize the risk factors for kidney injury in this population and mitigate these risks. In this paper, the authors provide an overview of kidney disease pertaining to heart and liver transplantation in children with guidance on monitoring, diagnosis, prevention, and management.