Risk Of ESKD Research Articles

Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data.

Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.

Risk of ESKD in Older Live Kidney Donors with Hypertension.

Hypertension in older kidney donor candidates is viewed as safe. However, hypertension guidelines have evolved and long-term outcomes have not been explored. We sought to quantify the 15-year risk of ESKD and mortality in older donors (≥50 years old) with versus those without hypertension. A United States cohort of 24,533 older donors from 1999 to 2016, including 2265 with predonation hypertension, were linked to Centers for Medicare and Medicaid Services data and the Social Security Death Master File to ascertain ESKD development and mortality. The exposure of interest was predonation hypertension. From 2004 to 2016, hypertension was defined as documented predonation use of antihypertensive therapy, regardless of systolic BP or diastolic BP; from 1999 to 2003, when there was no documentation of antihypertensive therapy, hypertension was defined as predonation systolic BP ≥140 or diastolic BP ≥90 mm Hg. Older donors were 82% white, 6% black, 7% Hispanic, and 3% Asian. The median follow-up was 7.1 years (interquartile range, 3.4-11.1; maximum, 18). There were 24 ESKD and 252 death events during the study period. The 15-year risk of ESKD was 0.8% (95% confidence interval [95% CI], 0.4 to 1.6) for donors with hypertension (mean systolic BP, 138 mm Hg) versus 0.2% (95% CI, 0.1 to 0.4) for donors without hypertension (mean systolic BP, 123 mm Hg; adjusted hazard ratio, 3.04; 95% CI, 1.28 to 7.22; P=0.01). When predonation antihypertensive therapy was available, the risk of ESKD was 6.21-fold higher (95% CI, 1.20 to 32.17; P=0.03) for donors using antihypertensive therapy (mean systolic BP, 132 mm Hg) versus those not using antihypertensive therapy (mean systolic BP, 124 mm Hg). There was no significant association between donor hypertension and 15-year mortality (hazard ratio, 1.18; 95% CI, 0.84 to 1.66; P=0.34). Compared with older donors without hypertension, older donors with hypertension had higher risk of ESKD, but not mortality, for 15 years postdonation. However, the absolute risk of ESKD was small.

Effects of Treatment of Metabolic Acidosis in CKD: A Systematic Review and Meta-Analysis.

Metabolic acidosis is associated with progression of CKD and has significant adverse effects on muscle and bone. A systematic review and meta-analysis was conducted to evaluate the benefits and risks of metabolic acidosis treatment with oral alkali supplementation or a reduction of dietary acid intake in those with CKD. MEDLINE, Embase, and Cochrane CENTRAL were searched for relevant trials in patients with stage 3-5 CKD and metabolic acidosis (<22 mEq/L) or low-normal serum bicarbonate (22-24 mEq/L). Data were pooled in a meta-analysis with results expressed as weighted mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs), using a random effects model. Study quality and strength of evidence were assessed using Cochrane risk of bias and the Grading of Recommendations Assessment, Development and Evaluation criteria. Fourteen clinical trials were included (n=1394 participants). Treatment of metabolic acidosis with oral alkali supplementation or a reduction of dietary acid intake increased serum bicarbonate levels (14 studies, 1378 patients, mean difference 3.33 mEq/L, 95% CI, 2.37 to 4.29) and resulted in a slower decline in eGFR (13 studies, 1329 patients, mean difference -3.28 ml/min per 1.73 m2, 95% CI, -4.42 to -2.14; moderate certainty) and a reduction in urinary albumin excretion (very-low certainty), along with a reduction in the risk of progression to ESKD (relative risk, 0.32; 95% CI, 0.18 to 0.56; low certainty). Oral alkali supplementation was associated with worsening hypertension or the requirement for increased antihypertensive therapy (very-low certainty). Low-to-moderate certainty evidence suggest that oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline and potentially reduce the risk of ESKD in patients with CKD and metabolic acidosis.

Risks of Living Kidney Donation: Current State of Knowledge on Outcomes Important to Donors.

In the past decade, there have been increasing efforts to better define and quantify the short- and long-term risks of living kidney donation. Recent studies have expanded upon the previous literature by focusing on outcomes that are important to potential and previous donors, applying unique databases and/or registries to follow large cohorts of donors for longer periods of time, and comparing outcomes with healthy nondonor controls to estimate attributable risks of donation. Leading outcomes important to living kidney donors include kidney health, surgical risks, and psychosocial effects of donation. Recent data support that living donors may experience a small increased risk of severe CKD and ESKD compared with healthy nondonors. For most donors, the 15-year risk of kidney failure is <1%, but for certain populations, such as young, black men, this risk may be higher. New risk prediction tools that combine the effects of demographic and health factors, and innovations in genetic risk markers are improving kidney risk stratification. Minor perioperative complications occur in 10%-20% of donor nephrectomy cases, but major complications occur in <3%, and the risk of perioperative death is <0.03%. Generally, living kidney donors have similar or improved psychosocial outcomes, such as quality of life, after donation compared with before donation and compared with nondonors. Although the donation process should be financially neutral, living kidney donors may experience out-of-pocket expenses and lost wages that may or may not be completely covered through regional or national reimbursement programs, and may face difficulties arranging subsequent life and health insurance. Living kidney donors should be fully informed of the perioperative and long-term risks before making their decision to donate. Follow-up care allows for preventative care measures to mitigate risk and ongoing surveillance and reporting of donor outcomes to inform prior and future living kidney donors.

Blood Pressure Goals in Patients with CKD: A Review of Evidence and Guidelines.

Hypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade, a number of hypertension guidelines have been published with varying recommendations for BP goals in patients with CKD. Most recently, the American College of Cardiology/American Heart Association 2017 hypertension guidelines set a BP goal of <130/80 mm Hg for patients with CKD and others at elevated cardiovascular risk. These guidelines were heavily influenced by the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which documented that an intensive BP goal to a systolic BP <120 mm Hg decreased the risk of cardiovascular disease and mortality in nondiabetic adults at high cardiovascular risk, many of whom had CKD; the intensive BP goal did not retard CKD progression. It is noteworthy that SPRINT measured BP with automated devices (5-minute wait period, average of three readings) often without observers, a technique that potentially results in BP values that are lower than what is typically measured in the office. Still, results from SPRINT along with long-term follow-up data from the Modification of Diet in Renal Disease and the African American Study of Kidney Disease and Hypertension suggest that a BP goal <130/80 mm Hg will reduce mortality in patients with CKD. Unfortunately, data are more limited in patients with diabetes or stage 4-5 CKD. Increased adverse events, including electrolyte abnormalities and decreased eGFR, necessitate careful laboratory monitoring. In conclusion, a BP goal of <130/80 is a reasonable, evidence-based BP goal in patients with CKD. Implementation of this intensive BP target will require increased attention to measuring BP accurately, assessing patient preferences and concurrent medical conditions, and monitoring for adverse effects of therapy.

Association of Monoclonal Gammopathy with Progression to ESKD among US Veterans.

Whether patients with monoclonal protein are at a higher risk for progression of kidney disease is not known. The goal of this study was to measure the association of monoclonal protein with progression to ESKD. This was a retrospective cohort study of 2,156,317 patients who underwent serum creatinine testing between October 1, 2000 and September 30, 2001 at a Department of Veterans Affairs medical center, among whom 21,898 had paraprotein testing within 1 year before or after cohort entry. Progression to ESKD was measured using linked data from the US Renal Data System. Overall, 1,741,707 cohort members had an eGFR≥60 ml/min per 1.73 m2, 283,988 had an eGFR of 45-59 ml/min per 1.73 m2, 103,123 had an eGFR of 30-44 ml/min per 1.73 m2 and 27,499 had an eGFR of 15-29 ml/min per 1.73 m2. The crude incidence of ESKD ranged from 0.7 to 80 per 1000 person-years from the highest to lowest eGFR category. Patients with low versus preserved eGFR were more likely to be tested for monoclonal protein but no more likely to have a positive test result. In adjusted analyses, a positive versus negative test result was associated with a higher risk of ESKD among patients with an eGFR≥60 ml/min per 1.73 m2 (hazard ratio, 1.67; 95% confidence interval, 1.22 to 2.29) and those with an eGFR of 15-29 ml/min per 1.73 m2 (hazard ratio, 1.38; 95% confidence interval, 1.07 to 1.77), but not among those with an eGFR of 30-59 ml/min per 1.73 m2. Progression to ESKD was attributed to a monoclonal process in 21 out of 76 versus seven out of 174 patients with monoclonal protein and preserved versus severely reduced eGFR at cohort entry. The detection of monoclonal protein provides little information on ESKD risk for most patients with a low eGFR. Further study is required to better understand factors contributing to a positive association of monoclonal protein with ESKD risk in patients with preserved and severely reduced levels of eGFR.

End-Stage Kidney Disease following Surgical Management of Kidney Cancer.

We investigated the incidence of ESKD after surgical management of kidney cancer in the Australian state of Queensland, and described patterns in the initiation of kidney replacement therapy resulting from kidney cancer across Australia. All newly diagnosed cases of kidney cancer in the Australian state of Queensland between January of 2009 and December of 2014 were ascertained through the Queensland Cancer Registry. There were 2739 patients included in our analysis. Patients who developed ESKD were identified using international classification of disease-10-coded hospital administrative data. Incidence rate and 3-year cumulative incidence were calculated, and multivariable Cox proportional hazards models were used to identify factors associated with ESKD. Additional descriptive analysis was undertaken of Australian population data. The incidence rate of ESKD in all patients was 4.9 (95% confidence interval [95% CI], 3.9 to 6.2) per 1000 patient-years. The 3-year cumulative incidence was 1.7%, 1.9%, and 1.0% for all patients, and patients managed with radical or partial nephrectomy, respectively. Apart from preoperative kidney disease, exposures associated with increased ESKD risk were age≥65 years (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, 2.3; 95% CI, 1.3 to 4.3), preoperative diabetes (aHR, 1.8; 95% CI, 1.0 to 3.3), American Society of Anesthesiologists classification ≥3 (aHR, 4.0; 95% CI, 2.2 to 7.4), socioeconomic disadvantage (aHR, 1.6; 95% CI, 0.9 to 2.7), and postoperative length of hospitalization ≥6 days (aHR, 2.1; 95% CI, 1.4 to 3.0). Australia-wide trends indicate that the rate of kidney replacement therapy after oncologic nephrectomy doubled between 1995 and 2015, from 0.3 to 0.6 per 100,000 per year. In Queensland between 2009 and 2014, one in 53 patients managed with radical nephrectomy and one in 100 patients managed with partial nephrectomy developed ESKD within 3 years of surgery. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_28_CJASNPodcast_18_1_.mp3.

Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD.

Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria. Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death. At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02). Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.