Life Years Lost in Children with Kidney Failure: A Binational Cohort Study with Multistate Probabilities of Death and Life Expectancy.

SIGNIFICANCE STATEMENT: In children with kidney failure, little is known about their treatment trajectories or the effects of kidney failure on lifetime survival and years of life lost, which are arguably more relevant measures for children. In this population-based cohort study of 2013 children who developed kidney failure in Australia and New Zealand, most children were either transplanted after initiating dialysis (74%) or had a preemptive kidney transplant (14%). Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The expected (compared with the general population) number of life years lost ranged from 16 to 32 years, with female patients and those who developed kidney failure at a younger age experiencing the greatest loss of life years. BACKGROUND: Of the consequences of kidney failure in childhood, those rated as most important by children and their caregivers are its effects on long-term survival. From a life course perspective, little is known about the experience of kidney failure treatment or long-term survival. METHODS: To determine expected years of life lost (YLL) and treatment trajectory for kidney failure in childhood, we conducted a population-based cohort study of all children aged 18 years or younger with treated kidney failure in Australia (1980-2019) and New Zealand (1988-2019).We used patient data from the CELESTIAL study, which linked the Australian and New Zealand Dialysis and Transplant registry with national death registers. We estimated standardized mortality ratios and used multistate modeling to understand treatment transitions and life expectancy. RESULTS: A total of 394 (20%) of 2013 individuals died over 30,082 person-years of follow-up (median follow-up, 13.1 years). Most children (74%) were transplanted after initiating dialysis; 14% (18% of male patients and 10% of female patients) underwent preemptive kidney transplantation. Excess deaths (compared with the general population) decreased dramatically from 1980 to 1999 (from 41 to 22 times expected) and declined more modestly (to 17 times expected) by 2019. Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The number of YLL ranged from 16 to 32 years, with the greatest loss among female patients and those who developed kidney failure at a younger age. CONCLUSIONS: Children with kidney failure lose a substantial number of their potential life years. Female patients and those who develop kidney failure at younger ages experience the greatest burden.

The impact of comorbid chronic kidney disease and diabetes on health-related quality-of-life: a 12-year community cohort study.

BACKGROUND: Quality-of-life is an essential outcome for clinical care. Both chronic kidney disease (CKD) and diabetes have been associated with poorer quality-of-life. The combined impact of having both diseases is less well understood. As diabetes is the most common cause of CKD, it is imperative that we deepen our understanding of their joint impact. METHODS: This was a prospective, longitudinal cohort study of community-based Australians aged ≥25 years who participated in the Australian Diabetes, Obesity and Lifestyle study. Quality-of-life was measured by physical component summary (PCS) and mental component summary sub-scores of the Short Form (36) Health Survey. Univariate and multivariate linear mixed effect regressions were performed. RESULTS: Of the 11 081 participants with quality-of-life measurements at baseline, 1112 had CKD, 1001 had diabetes and of these 271 had both. Of the 1112 with CKD 421 had Stage 1, 314 had Stage 2, 346 had Stage 3 and 31 had Stages 4/5. Adjusted linear mixed effect models showed baseline PCS was lower for those with both CKD and diabetes compared with either disease alone (P < 0.001). Longitudinal analysis demonstrated a more rapid decline in PCS in those with both diseases. CONCLUSIONS: The combination of CKD and diabetes has a powerful adverse impact on quality-of-life, and participants with both diseases had significantly poorer quality-of-life than those with one condition.

The impact of progressive chronic kidney disease on health-related quality-of-life: a 12-year community cohort study.

PURPOSE: Quality-of-life is poor in end-stage kidney disease; however, the relationships between earlier stages of chronic kidney disease (CKD) and are poorly understood. This study explored longitudinal quality-of-life changes in a community-based CKD cohort and assessed associations between CKD and quality-of-life over time, and between baseline quality-of-life and CKD outcomes. METHODS: We used the Australian diabetes, obesity and lifestyle study-a nationally representative, prospective cohort with data collected at baseline, year 5 and year 12-to examine the relationships between CKD stage, quality-of-life and outcomes. Linear mixed regression, cox proportional hazards, Kaplan-Meier and competing risks analyses were used. RESULTS: Of 1112 participants with CKD and baseline quality-of-life data, the physical component summary (PCS) score was significantly lower than for the general population (p = 0.01 age and sex adjusted), while the mental component summary (MCS) score was no different (p = 0.9 age and sex adjusted). In our unadjusted mixed effects model, more advanced kidney disease was associated with lower PCS and higher MCS at baseline (p < 0.001 and p < 0.01, respectively); however, this effect was no longer significant after adjustment for demographic and clinical variables. The rate of decline in PCS over the period of follow-up was greatest for those with more advanced kidney disease (p < 0.001 in unadjusted model, p = 0.007 in adjusted model). There was no association between change in MCS over the period of follow-up and severity of kidney disease in either the unadjusted or adjusted model (p = 0.7 and p = 0.1, respectively). Lower PCS, but not MCS, was associated with increased cardiovascular and increased all-cause mortality even after adjustment for key demographic and clinical variables (p < 0.001). CONCLUSIONS: Physical, but not mental, quality-of-life is significantly impaired in CKD, and continues to decline with disease progression.

Physical component quality of life reflects the impact of time and moderate chronic kidney disease, unlike SF-6D utility and mental component SF-36 quality of life: An AusDiab analysis.

AIM: Assessing the impact of interventions on the patient experience requires measures that are plausibly responsive to change. In a community cohort of people with and without chronic kidney disease (CKD) markers at baseline, we aimed to evaluate change in commonly used measures of quality of life (QOL) over the passage of 5 years. METHODS: Included were 6400 participants in the Australian Diabetes, Obesity and Lifestyle (AusDiab) surveys with baseline and 5-year CKD and QOL measures. Changes in SF-6D utility, and the Medical Outcomes Study 36-Item Short Form (SF-36) physical (PCS) and mental (MCS) component summary scores, were evaluated with regression analyses according to the baseline presence of reduced estimated glomerular filtration rate (eGFR) (CKD-Epidemiology Collaboration eGFR ≤60 m/min per 1.73 m2 ) or albuminuria (urine albumin:creatinine ratio ≥3.4 mg/mmol). RESULTS: At baseline, eGFR was reduced in 2.4% of participants and 5.1% had albuminuria. Participants with reduced eGFR had a lower SF-6D and PCS, and those with albuminuria a lower PCS, compared with those without, but the differences were explained by known confounders. MCS scores were not affected by the presence of reduced eGFR or albuminuria. Over 5 years all groups exhibited stable SF-6D and MCS scores but declining unadjusted PCS scores. PCS decline was greater for those with reduced eGFR, and remained significant after adjustment (-2.7 (-4.1 to -1.3) vs. -0.8 (-1.1 to -0.6, P < 0.01). Analyses according to CKD stages were essentially unchanged. CONCLUSION: Utility and mental QOL appears stable over 5 years, unaffected by time or markers of CKD health. Physical QOL appeared to deteriorate with time, especially for those with CKD, making it a more likely candidate assessment measure for intervention and health service evaluations.

Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding.

PURPOSE: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. METHOD: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. FINDINGS: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. DISCUSSION: To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. CONCLUSION: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.

Sex-Based Differences in Risk Factors and Complications of Chronic Kidney Disease.

Globally, females are ∼30% more likely to have pre-dialysis chronic kidney disease (CKD) than males for reasons that are not fully understood. CKD is associated with numerous adverse health outcomes which makes understanding and working to eradicating sex based disparities in CKD prevalence essential. This review maps both what is known, and what is unknown, about the way sex and gender impacts (1) the epidemiology and risk factors for CKD including age, diabetes, hypertension, obesity, smoking, and cerebrovascular disease, and (2) the complications from CKD including kidney disease progression, cardiovascular disease, CKD mineral and bone disorders, anaemia, quality-of-life, cancer and mortality. This mapping can be used to guide future research.

Cardiac Mortality in Kidney Transplant Patients: A Population-based Cohort Study 1988-2013 in Australia and New Zealand.

BACKGROUND: Transplant recipients experience excess cardiac mortality. We compared circulatory death rates in Australian and New Zealand kidney transplant recipients to the general population and identified risk factors for circulatory death in kidney transplant recipients. METHODS: The primary cause of death for kidney transplant recipients aged ≥18 was established through ICD-10-AM codes using data linkage between the Australia and New Zealand dialysis and transplant registry and national death registers. We estimated standardized mortality ratios (SMRs) and developed a Fine-Gray competing risks model to determine risk factors for cardiac mortality. RESULTS: Of 5089 deaths in 16 329 kidney transplant recipients (158 325 person-years), 918 (18%) were cardiac. An increased risk of circulatory death was associated with older age (P < 0.001), male sex (P < 0.001), longer dialysis duration (P = 0.004), earlier era of transplantation (P < 0.001), ever graft failure (P < 0.001), known coronary artery disease (P = 0.002), and kidney failure from diabetes or hypertension (P < 0.001). The cardiac SMR was 5.4 [95% confidence interval (CI): 5.0-5.8], falling from 8.0 (95% CI: 4.9-13.1) in 1988 to 5.3 (95% CI: 4.0-7.0) in 2013 (P < 0.001). Females, particularly young ones, had significantly higher relative cardiac mortality than men. In recipients aged 40 years, the cardiac SMR was 26.5 (95% CI: 15.0-46.6) in females and 7.5 (95% CI: 5.0-11.1) for males. CONCLUSIONS: Cardiac risks remain elevated in kidney transplant recipients and may be under-recognized, and prevention and treatment interventions less accessed, less effective or even harmful in female recipients.

Recurrent IgA Nephropathy After Kidney Transplantation.

Large numbers of patients with end-stage kidney disease caused by IgA nephropathy are transplanted every year, and each of these patients faces the risk of recurrence in their kidney graft. We review the epidemiology, diagnosis, and outcomes of recurrent IgA nephropathy. Mechanistic insights, therapeutic options, and knowledge gaps are reviewed, and we discuss future options to better understand and manage this disorder.

Pregnancy outcomes for kidney transplant recipients with transplantation as a child.

IMPORTANCE: Pregnancy outcomes for women who received a kidney transplant in childhood are uncertain. OBJECTIVES: To report pregnancy outcomes for women with kidney transplantation in childhood (aged <18 years; child-tx mothers) and to compare them with those for women who received a kidney transplant in adulthood (aged ≥18 years; adult-tx mothers). DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study in Australia and New Zealand of all women with a functioning kidney transplant included in the Australia and New Zealand Dialysis and Transplant Registry for whom at least 1 pregnancy was reported between January 1, 1963, and December 31, 2012. MAIN OUTCOMES AND MEASURES: Pregnancy outcomes including live birth rates, gestational age, and proportion of babies who are small for gestational age. RESULTS: A total of 101 pregnancies in 66 child-tx mothers and 626 pregnancies in 401 adult-tx mothers were reported. At the time of pregnancy, child-tx mothers had a mean age of 25 (95% CI, 24-26) years with a functioning transplant for 10 (95% CI, 9-11) years, while adult-tx mothers had a mean age of 31 (95% CI, 31-31) years with a functioning transplant for 6 (95% CI, 5-6) years (both P < .001). Live births occurred in 76% of pregnancies in child-tx mothers and 77% of pregnancies in adult-tx mothers. The mean gestational ages were similar between child-tx and adult-tx mothers (35 [95% CI, 33-37] vs 36 [95% CI, 35-36] weeks, respectively; P = .68). The incidence of prematurity (<37 weeks' gestation) was also similar (child-tx mothers, 45%; adult-tx mothers, 53%). A similar proportion of preterm babies born to child-tx and adult-tx mothers were small for gestational age (22% vs 10%, respectively; odds ratio [OR] = 2.53 [95% CI, 1.13-5.69]). Term babies born to child-tx and adult-tx mothers were frequently small for gestational age (57% vs 38%, respectively; OR = 2.16 [95% CI, 1.23-3.81]), both significantly more frequently than babies born at term in the general population (child-tx mothers, OR = 11.93 [95% CI, 5.56-25.61]; adult-tx mothers, OR = 5.52 [95% CI, 2.56-11.89]). CONCLUSIONS AND RELEVANCE: Pregnancy outcomes for child-tx mothers are similar to those for adult-tx mothers, with no difference in the rate of live births, gestational age, or small for gestational age. Regardless of when women received their kidney transplant, their pregnancies are likely to result in a live, albeit preterm, birth. This work should provide comfort to child-tx mothers and their physicians that their early onset of kidney failure and longer period of transplantation and immunosuppression do not adversely affect their pregnancy outcomes compared with adult-tx mothers.