Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study

<p>Abstract</p> <p>Background</p> <p>To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care.</p> <p>Methods</p> <p>In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1^st2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT.</p> <p>Results</p> <p>A total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m²/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m²/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m²/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m²/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful.</p> <p>Conclusions</p> <p>In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT.</p

Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease The Kompas Randomized Clinical Trial

Importance Prevention of postcontrast acute kidney injury in patients with stage 3 chronic kidney disease (CKD) by means of prehydration has been standard care for years. However, evidence for the need for prehydration in this group is limited. Objective To assess the renal safety of omitting prophylactic prehydration prior to iodine-based contrast media administration in patients with stage 3 CKD. Design, Setting, and Participants The Kompas trial was a multicenter, noninferiority, randomized clinical trial conducted at 6 hospitals in the Netherlands in which 523 patients with stage 3 CKD were randomized in a 1:1 ratio to receive no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate administered in a 1-hour infusion before undergoing elective contrast-enhanced computed tomography from April 2013 through September 2016. Final follow-up was completed in September 2017. Data were analyzed from January 2018 to June 2019. Interventions In total, 262 patients were allocated to the no prehydration group and 261 were allocated to receive prehydration. Analysis on the primary end point was available in 505 patients (96.6%). Main Outcomes and Measures The primary end point was the mean relative increase in serum creatinine level 2 to 5 days after contrast administration compared with baseline (noninferiority margin of less than 10% increase in serum creatinine level). Secondary outcomes included the incidence of postcontrast acute kidney injury 2 to 5 days after contrast administration, mean relative increase in creatinine level 7 to 14 days after contrast administration, incidences of acute heart failure and renal failure requiring dialysis, and health care costs. Results Of 554 patients randomized, 523 were included in the intention-to-treat analysis. The median (interquartile range) age was 74 (67-79) years; 336 (64.2%) were men and 187 (35.8%) were women. The mean (SD) relative increase in creatinine level 2 to 5 days after contrast administration compared with baseline was 3.0% (10.5) in the no prehydration group vs 3.5% (10.3) in the prehydration group (mean difference, 0.5; 95% CI, -1.3 to 2.3; P <.001 for noninferiority). Postcontrast acute kidney injury occurred in 11 patients (2.1%), including 7 of 262 (2.7%) in the no prehydration group and 4 of 261 (1.5%) in the prehydration group, which resulted in a relative risk of 1.7 (95% CI, 0.5-5.9; P = .36). None of the patients required dialysis or developed acute heart failure. Subgroup analyses showed no evidence of statistical interactions between treatment arms and predefined subgroups. Mean hydration costs were euro119 (US $143.94) per patient in the prehydration group compared with euro0 (US$0) in the no prehydration group (P <.001). Other health care costs were similar. Conclusions and Relevance Among patients with stage 3 CKD undergoing contrast-enhanced computed tomography, withholding prehydration did not compromise patient safety. The findings of this study support the option of not giving prehydration as a safe and cost-efficient measure

A joint latent class changepoint model to improve the prediction of time to graft failure

The reciprocal of serum creatinine concentration, RC, is often used as a biomarker to monitor renal function. It has been observed that RC trajectories remain relatively stable after transplantation until a certain moment, when an irreversible decrease in the RC levels occurs. This decreasing trend commonly precedes failure of a graft. Two subsets of individuals can be distinguished according to their RC trajectories: a subset of individuals having stable RC levels and a subset of individuals who present an irrevocable decrease in their RC levels. To describe such data, the paper proposes a joint latent class model for longitudinal and survival data with two latent classes. RC trajectories within latent class one are modelled by an intercept-only random-effects model and RC trajectories within latent class two are modelled by a segmented random changepoint model. A Bayesian approach is used to fit this joint model to data from patients who had their first kidney transplantation in the Leiden University Medical Center between 1983 and 2002. The resulting model describes the kidney transplantation data very well and provides better predictions of the time to failure than other joint and survival model

A joint latent class changepoint model to improve the prediction of time to graft failure

The reciprocal of serum creatinine concentration, RC, is often used as a biomarker to monitor renal function. It has been observed that RC trajectories remain relatively stable after transplantation until a certain moment, when an irreversible decrease in the RC levels occurs. This decreasing trend commonly precedes failure of a graft. Two subsets of individuals can be distinguished according to their RC trajectories: a subset of individuals having stable RC levels and a subset of individuals who present an irrevocable decrease in their RC levels. To describe such data, the paper proposes a joint latent class model for longitudinal and survival data with two latent classes. RC trajectories within latent class one are modelled by an intercept-only random-effects model and RC trajectories within latent class two are modelled by a segmented random changepoint model. A Bayesian approach is used to fit this joint model to data from patients who had their first kidney transplantation in the Leiden University Medical Center between 1983 and 2002. The resulting model describes the kidney transplantation data very well and provides better predictions of the time to failure than other joint and survival models. Copyright 2008 Royal Statistical Society.

Predicting kidney graft failure using time-dependent renal function covariates

Chronic rejection and recurrent disease are the major causes of late graft failure in renal transplantation. To assess outcome, most researchers use Cox proportional hazard analysis with time-fixed covariates. We developed a model adding time-dependent renal function covariates to improve the prediction of late graft failure. We studied 692 kidney transplants at the Leiden University Medical Center that had functioned for at least 6 months. Graft failure from chronic rejection or recurrent disease occurred in 106 patients. The reciprocal of last recorded serum creatinine (RC), the ratio of RC and RC at 6 months (RC6), and the time elapsed since last observation (TEL) were used as time-dependent covariates. Cadaveric donor transplantation, a lower RC, and a lower ratio of RC/RC6 were independently associated with graft failure. The impact of the last recorded RC was dependent on its value, TEL, and the time since transplantation. Validation of the model confirmed much higher failure predictions in those with subsequent graft failure compared with nonfailures. This study illustrates that the prediction of late graft failure could be improved significantly by using time-dependent renal function covariate

Chronic rejection with or without transplant vasculopathy

BACKGROUND: Chronic allograft nephropathy (CAN) is defined and graded in the Banff '97 scheme by the severity of interstitial fibrosis and tubular atrophy. It has been denoted that chronic rejection can be diagnosed if the typical vascular lesions are seen, consisting of fibrointimal thickening. We observed several patients who developed CAN without vascular changes or signs of cyclosporine toxicity. Therefore, we assessed the risk factor profiles of CAN with and without transplant vasculopathy. METHODS: A cohort of 654 cadaveric renal transplants performed between 1983 and 1997 that functioned for more than 6 months was studied. Fifty-four transplants had CAN defined by a significant decline in renal function together with interstitial fibrosis and tubular atrophy without signs of cyclosporine nephrotoxicity or recurrent disease. Using the Banff chronic vascular (CV) score, 23 of 54 cases (43%) had a chronic vasculopathy score of 0 or 1 whereas 31 cases (57%) had a CV score of 2 or 3. Applying multivariate logistic regression, predictor variables of the two groups were compared with 231 transplants with a stable function for at least 5 yr. RESULTS: Graft histology was obtained at a mean of 2.4 and 2.9 yr after transplantation in the group with or without vasculopathy, respectively. Acute rejection episodes (AREs) after 3 months post-transplantation were the strongest risk factor for both forms of CAN, odds ratio (OR) 14.7 (6.0-36.0). CAN with vasculopathy was also associated with transplants performed in the 1980s, OR 4.95 (1.65-14.9) and with creatinine clearance at 6 months, OR 0.58 (0.44-0.75) per 10 mL/min increase. In contrast, young recipient age, OR 0.69 (0.47-0.99) per 10-yr increase, and the presence of panel reactive antibodies at the time of transplantation, OR 1.26 (1.08-1.47) per 10% increase, were independent risk factors for CAN without vasculopathy. CONCLUSIONS: After exclusion of cyclosporine toxicity or recurrent disease CAN occurred without moderate or severe transplant vasculopathy in 43% of the cases. The correlation with young recipient age, sensitization and late ARE suggest an immune pathogenesis, consistent with chronic rejectio

Large health disparities in cardiovascular death in men and women, by ethnicity and socioeconomic status in an urban based population cohort.

Background: Socioeconomic status and ethnicity are not incorporated as predictors in country-level cardiovascular risk charts on mainland Europe. The aim of this study was to quantify the sex-specific cardiovascular death rates stratified by ethnicity and socioeconomic factors in an urban population in a universal healthcare system. Methods: Age-standardized death rates (ASDR) were estimated in a dynamic population, aged 45–75 in the city of The Hague, the Netherlands, over the period 2007–2018, using data of Statistics Netherlands. Results were stratified by sex, ethnicity (country of birth) and socioeconomic status (prosperity) and compared with a European cut-off for high-risk countries (ASDR men 225/100,000 and women 175/100,000). Findings: In total, 3073 CVD deaths occurred during 1·76 million person years follow-up. Estimated ASDRs (selected countries of birth) ranged from 126 (95%CI 89–174) in Moroccan men to 379 (95%CI 272–518) in Antillean men, and from 86 (95%CI 50–138) in Moroccan women to 170 (95%CI 142–202) in Surinamese women. ASDRs in the highest and lowest prosperity quintiles were 94 (95%CI 90–98) and 343 (95%CI 334–351) for men, and 43 (95%CI 41–46) and 140 (95%CI 135–145), for women, respectively. Interpretation: In a diverse urban population, large health disparities in cardiovascular ASDRs exists across ethnic and socioeconomic subgroups. Identifying these high-risk subgroups followed by targeted preventive efforts, might provide a basis for improving cardiovascular health equity within communities. Instead of classifying countries as high-risk or low-risk, a shift towards focusing on these subgroups within countries might be needed. Funding: Leiden University Medical Center and Leiden Universit

Trial profile.

<p>Trial profile.</p

Randomized trial of one-hour sodium bicarbonate vs standard periprocedural saline hydration in chronic kidney disease patients undergoing cardiovascular contrast procedures - Fig 2

<p><b>A)</b> Subgroup analyses on the primary outcome of a relative increase in serum creatinine 48–96 hours post intra-arterial contrast administration. Effect size is calculated as the difference in the mean relative increase in serum creatinine between both randomisation groups. <b>B)</b> Subgroup analyses on the secondary outcome of risk of contrast-induced acute kidney injury, calculated as relative risk. The straight line indicates the point estimate of the entire study population and the dashed line indicates no effect. Baseline creatinine clearance was calculated using the MDRD-formula.</p