Intensive Home Blood Pressure Lowering in Patients with Advanced CKD.

RATIONALE & OBJECTIVE: Optimal blood pressure (BP) targets in advanced CKD are controversial. More intensive BP lowering in the setting of advanced CKD is thought to be associated with risk of acute kidney injury, hyperkalemia, and ESKD. We aimed to conduct a pilot trial of intensive BP control to determine if lower SBP targets can be safely achieved for patients with CKD through titration of BP medications using in-home measured BP. STUDY DESIGN: Non-blinded randomized controlled trial. SETTINGS & PARTICIPANTS: 108 patients with advanced CKD (eGFR ≤30 mL/min/1.73 m2) and hypertension. INTERVENTIONS: Participants were randomized either to a target home SBP goal of <120 mmHg (N=66) or a less intensive SBP goal (N=42). Antihypertensive medications were titrated to achieve the target home SBP range in the first 4 months of the study and maintained until the end of the study. Home BP was measured using a wireless Bluetooth-enabled monitor that transmitted readings to providers in real-time. OUTCOMES: The primary efficacy outcome was the difference in achieved clinic SBP between the two study arms from months 4-12. Safety outcomes included hyperkalemia, a composite outcome of falls or syncope, and onset of need for dialysis or kidney transplantation. RESULTS: The mean clinic SBP at month 12 was 124.7 mmHg in the intensive SBP group vs. 138.2 mmHg in the less intensive SBP group. Averaged over months 4-12, the achieved mean clinic SBP in the intensive SBP arm was 11.7 mmHg (95% CI 7.5 to 16 mmHg, p<0.001) lower than the mean SBP achieved in the less intensive SBP arm. Primary safety outcomes were not statistically significantly different between the two arms (all p>0.05). LIMITATIONS: Small sample size which may limit our ability to detect clinically significant differences in rates of adverse outcomes; single-center design. CONCLUSIONS: A clinic SBP goal of <120 mmHg is feasible to achieve with the help of real-time home BP monitoring and appears to be safe in this study population with advanced CKD. Larger trials to determine optimal BP targets in advanced CKD and the risks and benefits associated with more intensive BP control are warranted.

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI.

BACKGROUND: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration. METHODS: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days). RESULTS: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively). CONCLUSION: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Acute kidney injury in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Colon Cancer Screening among Patients Receiving Dialysis in the United States: Are We Choosing Wisely?

The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.