Natriuretic Peptides in the Management of Solid Organ Transplantation Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis

Randomized controlled trials involving natriuretic peptide administration in solid organ transplantation setting have shown inconsistent effects for renal endpoints. We conducted a systematic review and meta-analysis of these trials to ascertain the role of natriuretic peptides in the management of solid organ transplantation associated acute kidney injury (AKI). MEDLINE, EMBASE, and Google scholar were searched independently by two authors for randomized trials evaluating renal effects of natriuretic peptides in solid organ transplantation settings. Two reviewers independently assessed the studies for eligibility and extracted the relevant data. The pooled estimate showed that natriuretic peptide administration is associated with a reduction in AKI requiring dialysis (odds ratio = 0.50 [0.26–0.97]), a statistically nonsignificant trend toward improvement in posttransplant creatinine clearance (weighted mean difference = 5.5 mL/min, [−1.3 to 12.2 mL/min]), and reduction in renal replacement requirement duration (weighted mean difference −44.0 hours, [−60.5 to −27.5 hours]). There were no mortality events and no adverse events related to natriuretic peptides. In conclusion, administration of natriuretic peptides in solid organ transplantation may be associated with significant improvements in renal outcomes. These observations need to be confirmed in an adequately powered, prospective multicenter study

Hospital Mortality in Critically Ill Patients

In a multicenter observational cohort of patients-admitted to intensive care units (ICU), we assessed whether creatinine elevation prior to dialysis initiation in acute kidney injury (AKI-D) further discriminates risk-adjusted mortality. AKI-D was categorized into four groups (Grp) based on creatinine elevation aer ICU admission but before dialysis initiation: Grp I > 0.3 mg/dL to <2-fold increase, Grp II ≥2 times but <3 times increase, Grp III ≥3-fold increase in creatinine, and Grp IV none or <0.3 mg/dl increase. Standardized mortality rates (SMR) were calculated by using a validated risk-adjusted mortality model and expressed with 95% con�dence intervals (CI). 2,744 patients developed AKI-D during ICU stay; 36.7%, 20.9%, 31.2%, and 11.2% belonged to groups I, II, III, and IV, respectively. SMR showed a graded increase in Grp I, II, and III (1.40 (95% CI, 1.29-1.42), 1.84 (1.66-2.04), and 2.25 (2.07-2.45)) and was 0.98 (0.78-1.20) in Grp IV. In ICU patients with AKI-D, degree of creatinine elevation prior to dialysis initiation is independently associated with hospital mortality. It is the lowest in those experiencing minor or no elevations in creatinine and may represent reversible �uid-electrolyte disturbances

Contrast-Induced Nephropathy in Renal Transplant Recipients: A Single Center Experience

BACKGROUND: Contrast-induced nephropathy (CIN) in native kidneys is associated with a significant increase in mortality and morbidity. Data regarding CIN in renal allografts are limited, however. We retrospectively studied CIN in renal allografts at our institution: its incidence, risk factors, and effect on long-term outcomes including allograft loss and death. METHODS: One hundred thirty-five renal transplant recipients undergoing 161 contrast-enhanced computed tomography (CT) scans or coronary angiograms (Cath) between years 2000 and 2014 were identified. Contrast agents were iso- or low osmolar. CIN was defined as a rise in serum creatinine (SCr) by \u3e0.3 mg/dl or 25% from baseline within 4 days of contrast exposure. After excluding 85 contrast exposures where patients had no SCr within 4 days of contrast administration, 76 exposures (CT: RESULTS: Incidence of CIN was 13% following both, CT (6 out of 45) and Cath (4 out of 31). Significant bivariate predictors of CIN were IV fluid administration ( CONCLUSION: CIN is common in kidney transplant recipients, and there is room for quality improvement with regards to careful renal function monitoring post-contrast exposure. In our study

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Functional status, pre-dialysis health and clinical outcomes among elderly dialysis patients

Abstract Background Elderly patients comprise the fastest growing population initiating dialysis in United States. The impact of poor functional status and pre-dialysis health status on clinical outcomes in elderly dialysis patients is not well studied. Methods We studied a retrospective cohort of 49,645 incident end stage renal disease patients that initiated dialysis between January 1, 2008 and December 31, 2008 from the United States Renal Data System with linked Medicare data covering at least 2 years prior to dialysis initiation. Using logistic regression models adjusted for pre-dialysis health status and other cofounders, we examined the impact of poor functional status as defined from form 2728 on 1-year all-cause mortality as primary outcome, type of dialysis modality (hemodialysis vs. peritoneal dialysis), and type of initial vascular access (arteriovenous access vs. central venous catheter) among hemodialysis patients as secondary outcomes. Results Mean age was 72 ± 11 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% had at least 1 pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. In adjusted analyses, 1-year mortality was higher in patients with poor functional status (OR, 1.48; 95% CI, 1.40–1.57). Adjusted odds of being initiated on hemodialysis than peritoneal dialysis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.16–1.66) were higher in patients with poor functional status. Poor functional status decreased the adjusted odds of starting hemodialysis with arteriovenous access as compared to central venous catheter (OR, 0.79; 95% CI, 0.72–0.86). Conclusion Poor functional status in elderly patients with end stage renal disease is associated with higher odds of initiating hemodialysis; increases the risk of central venous catheter use, and is an independent predictor of 1-year mortality

Contrast-Induced Nephropathy in Renal Transplant Recipients: A Single Center Experience

BackgroundContrast-induced nephropathy (CIN) in native kidneys is associated with a significant increase in mortality and morbidity. Data regarding CIN in renal allografts are limited, however. We retrospectively studied CIN in renal allografts at our institution: its incidence, risk factors, and effect on long-term outcomes including allograft loss and death.MethodsOne hundred thirty-five renal transplant recipients undergoing 161 contrast-enhanced computed tomography (CT) scans or coronary angiograms (Cath) between years 2000 and 2014 were identified. Contrast agents were iso- or low osmolar. CIN was defined as a rise in serum creatinine (SCr) by &gt;0.3 mg/dl or 25% from baseline within 4 days of contrast exposure. After excluding 85 contrast exposures where patients had no SCr within 4 days of contrast administration, 76 exposures (CT: n = 45; Cath: n = 31) in 50 eligible patients were analyzed. Risk factors assessed included demographics, comorbid conditions, type/volume of contrast agent used, IV fluids, N-acetylcysteine administration, and calcineurin inhibitor use. Bivariate and multivariable analyses were used to assess the risk of CIN.ResultsIncidence of CIN was 13% following both, CT (6 out of 45) and Cath (4 out of 31). Significant bivariate predictors of CIN were IV fluid administration (p = 0.05), lower hemoglobin (p = 0.03), and lower albumin (p = 0.02). In a multivariable model, CIN was predicted by N-acetylcysteine (p = 0.03) and lower hemoglobin (p = 0.01). Calcineurin inhibitor use was not associated with CIN. At last follow-up, CIN did not affect allograft or patient survival.ConclusionCIN is common in kidney transplant recipients, and there is room for quality improvement with regards to careful renal function monitoring post-contrast exposure. In our study, N-acetylcysteine exposure and lower hemoglobin were associated with CIN. Calcineurin inhibitor use was not associated with CIN. Our sample size is small, however, and larger prospective studies of CIN in renal allografts are needed

Cardiovascular outcomes in home hemodialysis and peritoneal dialysis patients

Key Points. Home hemodialysis is associated with decreased risk of stroke and acute coronary syndrome relative to peritoneal dialysis.Home hemodialysis is associated with decreased risk of cardiovascular death and all-cause death relative to peritoneal dialysis. Background. Cardiovascular disease is the leading cause of morbidity and mortality in patients with ESKD. Little is known about differences in cardiovascular outcomes between home hemodialysis (HHD) and peritoneal dialysis (PD). Methods. We evaluated 68,645 patients who initiated home dialysis between January 1, 2005, and December 31, 2018, using the United States Renal Data System with linked Medicare claims. Rates for incident cardiovascular events of acute coronary syndrome, heart failure, and stroke hospitalizations were determined. Using adjusted time-to-event models, the associations of type of home dialysis modality with the outcomes of incident cardiovascular events, cardiovascular death, and all-cause death were examined. Results. Mean age of patients in the study cohort was 64±15 years, and 42.3% were women. The mean time of follow-up was 1.8±1.6 years. The unadjusted cardiovascular event rate was 95.1 per thousand person-years (PTPY) (95% confidence interval [CI], 93.6 to 96.8), with a higher rate in patients on HHD than on PD (127.8 PTPY; 95% CI, 118.9 to 137.2 versus 93.3 PTPY; 95% CI, 91.5 to 95.1). However, HHD was associated with a slightly lower adjusted risk of cardiovascular events than PD (hazard ratio [HR], 0.92; 95% CI, 0.85 to 0.997). Compared with patients on PD, patients on HHD had 42% lower adjusted risk of stroke (HR, 0.58; 95% CI, 0.48 to 0.71), 17% lower adjusted risk of acute coronary syndrome (HR, 0.83; 95% CI, 0.72 to 0.95), and no difference in risk of heart failure (HR, 1.05; 95% CI, 0.94 to 1.16). HHD was associated with 22% lower adjusted risk of cardiovascular death (HR, 0.78; 95% CI, 0.71 to 0.86) and 8% lower adjusted risk of all-cause death (HR, 0.92; 95% CI, 0.87 to 0.97) as compared with PD. Conclusions. Relative to PD, HHD is associated with decreased risk of stroke, acute coronary syndrome, cardiovascular death, and all-cause death. Further studies are needed to better understand the factors associated with differences in cardiovascular outcomes by type of home dialysis modality in patients with kidney failure