Survival of South African patients on renal replacement therapy

CITATION: Jardine, T. et al. Survival of South African patients on renal replacement therapy. Clinical Kidney Journal, 13(5): 782–790. doi:10.1093/ckj/sfaa012The original publication is available at https://academic.oup.com/ckjBackground The majority of South Africans rely on a resource-constrained public healthcare sector, where access to renal replacement therapy (RRT) is strictly rationed. The incidence of RRT in this sector is only 4.4 per million population (pmp), whereas it is 139 pmp in the private sector, which serves mainly the 16% of South Africans who have medical insurance. Data on the outcomes of RRT may influence policies and resource allocation. This study evaluated, for the first time, the survival of South African patients starting RRT based on data from the South African Renal Registry. Methods The cohort included patients with end-stage kidney disease who initiated RRT between January 2013 and September 2016. Data were collected on potential risk factors for mortality. Failure events included stopping treatment without recovery of renal function and death. Patients were censored at 1 year or upon recovery of renal function or loss to follow-up. The 1-year patient survival was estimated using the Kaplan–Meier method and the association of potential risk factors with survival was assessed using multivariable Cox proportional hazards regression. Results The cohort comprised 6187 patients. The median age was 52.5 years, 47.2% had diabetes, 10.2% were human immunodeficiency virus (HIV) positive and 82.2% had haemodialysis as their first RRT modality. A total of 542 patients died within 1 year of initiating RRT, and overall 1-year survival was 90.4% [95% confidence interval (CI) 89.6–91.2]. Survival was similar in patients treated in the private sector as compared with the public healthcare sector [hazard ratio 0.93 (95% CI 0.72–1.21)]. Higher mortality was associated with older age and a primary renal diagnosis of ‘Other’ or ‘Aetiology unknown’. When compared with those residing in the Western Cape, patients residing in the Northern Cape, Eastern Cape, Mpumalanga and Free State provinces had higher mortality. There was no difference in mortality based on ethnicity, diabetes or treatment modality. The 1-year survival was 95.9 and 94.2% in HIV-positive and -negative patients, respectively. One-fifth of the cohort had no data on HIV status and the survival in this group was considerably lower at 77.1% (P < 0.001). Conclusions The survival rates of South African patients accessing RRT are comparable to those in better-resourced countries. It is still unclear what effect, if any, HIV infection has on survival.https://academic.oup.com/ckj/article/13/5/782/5780430Publishers versio

Predicting mortality after start of long-term dialysis-International validation of one- and two-year prediction models

BackgroundMortality prediction is critical on long-term kidney replacement therapy (KRT), both for individual treatment decisions and resource planning. Many mortality prediction models already exist, but as a major shortcoming most of them have only been validated internally. This leaves reliability and usefulness of these models in other KRT populations, especially foreign, unknown. Previously two models were constructed for one- and two-year mortality prediction of Finnish patients starting long-term dialysis. These models are here internationally validated in KRT populations of the Dutch NECOSAD Study and the UK Renal Registry (UKRR). MethodsWe validated the models externally on 2051 NECOSAD patients and on two UKRR patient cohorts (5328 and 45493 patients). We performed multiple imputation for missing data, used c-statistic (AUC) to assess discrimination, and evaluated calibration by plotting average estimated probability of death against observed risk of death. ResultsBoth prediction models performed well in the NECOSAD population (AUC 0.79 for the one-year model and 0.78 for the two-year model). In the UKRR populations, performance was slightly weaker (AUCs: 0.73 and 0.74). These are to be compared to the earlier external validation in a Finnish cohort (AUCs: 0.77 and 0.74). In all tested populations, our models performed better for PD than HD patients. Level of death risk (i.e., calibration) was well estimated by the one-year model in all cohorts but was somewhat overestimated by the two-year model. ConclusionsOur prediction models showed good performance not only in the Finnish but in foreign KRT populations as well. Compared to the other existing models, the current models have equal or better performance and fewer variables, thus increasing models' usability. The models are easily accessible on the web. These results encourage implementing the models into clinical decision-making widely among European KRT populations.Peer reviewe

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Long-Term Outcomes in IgA Nephropathy

BACKGROUND: IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope and lifetime risks for kidney failure. METHODS: The IgA nephropathy cohort (2,299 adults, 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy, plus proteinuria >0.5 g/day or eGFR <60 mL/min/1.73m 2 . Incident and prevalent populations were studied as well as a population representative of a typical phase 3 clinical trial cohort. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. RESULTS: Median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. Median (95% CI) kidney survival was 11.4 (10.5, 12.5) years; mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10-15 years. Based on eGFR and age at diagnosis, almost all patients are at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min/1.73m 2 /year can be maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and "clinical trial" populations. 30% of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the "clinical trial" population each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87-0.92). CONCLUSIONS: Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being "low-risk", with proteinuria <0.88 g/g (<100 mg/mmol), have high rates of kidney failure within 10 years