September 2018: Abstract Roundup


Study Underway to Examine Incidence of CKD after AKI in the ICU

Annals of Intensive Care.

Acute kidney injury (AKI) among patients in the intensive care unit (ICU) is associated with poor outcomes, including short- and long-term mortality, as well as increased risk of chronic kidney disease (CKD) in non-ICU patients. Guillaume Geri, MD, PhD, and colleagues recently described a prospective multicenter observational study designed to assess the incidence and determinants of CKD after AKI; the researchers are also seeking to develop a prediction score for CKD in ICU patients (NCT03282409).

The study will include 1200 patients who experienced AKI during a stay in the ICU and were discharged alive from the ICU. Patients will be monitored by a nephrologist at day 90 and every year for 3 years.

The primary outcome of interest is the occurrence of CKD, defined by a creatinine-based estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or renal replacement therapy for ESRD in patients whose eGFR will be normalized (≥60 mL/min/1.72 m2) at day 90. Secondary outcomes include changes in albuminuria, slope of decline in eGFR and risk of ESRD in patients with preexisting CKD, cardiovascular and thromboembolic events, and health-related quality of life.

According to the researchers, “This is the first study prospectively investigating kidney function evolution in ICU patients who suffered from AKI. Albuminuria and eGFR monitoring will allow identification of ICU patients at risk of CKD who may benefit from close surveillance after recovering from AKI. Major patient and AKI-related determinants will be tested to develop a prediction score for CKD in this population.”


Minimal Change Disease and Complications from AKI

Kidney International.

In 70% to 90% of nephrotic syndrome in children, the primary cause is minimal change disease; minimal change disease is also a cause of nephrotic syndrome in adults, including those >60 years of age. Because foot-process fusion impairs filtration of water and solutes, renal function is altered moderately in ~20% to 30% of patients. GFR is reduced by ~20% to 30% and returns to baseline with remission of proteinuria.

Previous studies have reported cases of AKI in approximately one-fifth to one -third of cases in adults without prior or concomitant renal disease. Male predominance is suggested by clinical attributes, as well as age >50 years, massive proteinuria, severe hypoalbuminemia, a background of hypertension, vascular lesions on kidney biopsy, and ischemic tubular necrosis.

Patients with AKI may require dialysis for weeks or months to achieve remission of proteinuria and resolution of oliguria. One explanation of tubular cell ischemic necrosis may be an effect of endothelin 1-induced vasoconstriction at the onset of proteinuria.

Some patients with AKI do not recover renal function. Among adults with minimal change disease, the primary factors associated with AKI are diuretic-induced hypovolemia and nephrotoxic agents. In the absence of intercurrent complications, AKI is uncommon in children. The primary risk factors are infection, nephrotoxic medication, and steroid resistance.

“In all patients, the goal of supportive therapy is essentially to buy time until glucocorticoids obtain emission of proteinuria, which allows resolution of renal failure,” the researchers said.



Tobacco Smoking among Patients with CKD and Risk of All-Cause Mortality

Clinical Journal of the American Society of Nephology. 2018;13(7):993-1001

Results of earlier studies have suggested an association between use of tobacco, alcohol, and illicit drugs and chronic kidney disease (CKD). Joshua D. Bundy, MPH, PhD, and colleagues conducted a study to examine the associations of substance use with progression of CKD and all-cause mortality among patients with CKD. The researchers utilized data from the Chronic Renal Insufficiency Cohort Study, a prospective, longitudinal study that included 3939 patients in the United States with CKD.

At baseline and at annual follow-up visits, self-reported data on tobacco smoking, alcohol use, marijuana use, and use of cocaine, heroin, or methamphetamine were obtained. Progression of CKD was defined as incident end-stage renal disease or halving of estimated glomerular filtration rate. To capture both recent and long-term use in multivariable time-dependent Cox regression, substance use was modeled as the cumulative average exposure.

Median follow-up was 5.5 years. During that time, 1287 participants developed CKD progression and 1001 died. At baseline, proportions of tobacco smoking were 13%, alcohol drinking 20%, marijuana use 33%, and hard illicit drug use 12%. Compared with nonsmoking throughout follow-up, multivariable adjusted hazard ratios (aHRs) for persistent tobacco smoking were 1.02 (95% confidence interval [CI], 0.86-1.21) for progression of CKD and 1.86 (95% CI, 1.54-2.24) for all-cause mortality.

Compared with nondrinking throughout the follow-up period, the aHRs for persistent alcohol drinking were 1.06 (95% CI, 0.88-1.29) for CKD progression and 0.73 (95% CI, 0.58-0.91) for all-cause mortality. Compared with nonuse throughout follow-up, the aHRs for persistent use of marijuana were 0.94 (95% CI, 0.82-1.07) for CKD progression and 1.11 (95% CI, 0.96-1.30) for all-cause mortality. Compared with nonuse throughout follow-up, the aHRs for persistent hard illicit drug use were 1.25 (95% CI, 1.00-1.55) for CKD progression and 1.41 (95% CI, 1.10-1.81) for all-cause mortality.

In summary, the researchers said, “Hard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD.”



Patients with Residual Kidney Function Benefit from Twice Weekly Dialysis

Journal of the American Society of Nephrology. 2018;29(7):1992-1999

The majority of patients on maintenance hemodialysis receive treatment three times per week, regardless of  residual kidney function due, in part, to uncertainty regarding how residual kidney function should be valued and incorporated into the dialysis prescription. More recently, guidelines have increased the weight given to residual kidney function, reducing the required treatment time in patients with residual function. The increase in weight assigned to residual renal function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion, according to researchers.

Sheldon C. Leong, MD, and colleagues conducted a study to determine whether plasma concentrations of secreted solutes are as well controlled in patients with residual function receiving hemodialysis twice weekly (n=9) as in anuric patients receiving hemodialysis three times per week (n=9).

The researchers measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate in both groups.

Compared with patients in the three-times per week group with the same standard Kt/Vurea, patients in the twice-weekly group had lower hippurate and phenylacetylglutamine concentrations. Concentrations of indoxyl sulfate and p-cresol sulfate were similar in both groups. The observed pattern of solute concentrations was accounted for by residual secretory function, as revealed on mathematical modeling.

In conclusion, the researchers said, “Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.”


Outcomes Differ with VHA Dialysis Center Use versus non-VHA Center

Clinical Journal of the American Society of Nephrology. 2018;13(7):1055-1062

Veterans with end-stage renal disease initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. There are few data available on differences in outcomes in patients based on the dialysis provider at initiation of treatment. Elani Streja, MPH, and colleagues conducted a study to examine the association between dialysis provider and mortality and hospitalization in US veterans initiating dialysis.

From 2007 to 2014, 68,727 US veterans initiated dialysis. The researchers examined the association of dialysis provider (VHA vs non-VHA) at treatment initiation with rates of mortality and hospitalization in the first 12 months following initiation. After accounting for demographics and comorbidities, the associations were examined across adjusted models.

Median age was 72 years, 5% were women, 24% were black, and 10% (n=7584) initiated dialysis at VHA dialysis centers. Patients who initiated treatment at VHA centers were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower estimated glomerular filtration rate at initiation. In fully adjusted models, patients in the VHA-center cohort were more likely to be hospitalized in the first 12 months of dialysis treatment (adjusted incidence rate ratio, 1.10; 95% confidence interval [CI], 1.07-1.14); risk of all-cause mortality was lower in that cohort (adjusted hazard ratio, 0.87; 95% CI, 0.83-0.93).

In conclusion, the researchers said, “Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units.”



Risk Factors of Rapid Correction of Severe Hyponatremia

Clinical Journal of the American Society of Nephrology. 2018;13(7):984-992

Serious complications, including osmotic demyelination, can result from rapid correction of severe hyponatremia. Jason C. George, MD, and colleagues conducted a study to examine the incidence and risk factors of rapid correction and osmotic demyelination. Rapid correction was defined as an increase in serum sodium of >8 mEq/L at 24 hours. Manual chart review of all available brain magnetic resonance imaging (MRI) reports determined osmotic demyelination.

Mean age of the cohort was 66 years, 55% were women, and 67% had prior hyponatremia (last outpatient sodium <135 mEq/L). At 24 hours, median change in serum sodium was 6.8 mEq/L and 606 patients (41%) had rapid correction. There were associations between younger age, being a woman, schizophrenia, lower Charlson comorbidity index, lower serum sodium at presentation, and urine sodium <30 mEq/L and greater risk of rapid correction. Lower risk of rapid correction was associated with prior hyponatremia, outpatient use of aldosterone antagonist, and being treated at an academic center.

Brain MRI reports were available on 20% of the cohort (n=295). Nine patients showed radiologic evidence of osmotic demyelination; eight had incident osmotic demyelination (five of whom had beer potomania), five had hypokalemia, and seven had sodium increase >8 mEq/L over a 24-hour period prior to MRI. Five patients with osmotic demyelination had apparent neurologic recovery.

“Among patients presenting with severe hyponatremia, rapid correction occurred in 41%; nearly all patients with incident osmotic demyelination had a documented episode of rapid correction,” the researchers said.



Clinical Evidence of the Association of BMI and Outcomes in Patients with ESRD

Progress in Cardiovascular Diseases.

Complications associated with obesity include diabetes, hypertension, cardiovascular disease, and premature death, but in certain populations, a link between obesity and increasing body mass index (BMI) and improved survival has been seen in observational studies. This obesity paradox or reverse epidemiology has been seen in clinical settings that include end-stage renal disease (ESRD).

Explanations to debunk the obesity paradox have included residual confounding in some studies; however, recent discoveries have provided biologically plausible mechanisms in which higher BMI can be linked to longevity in certain patient populations. Neda Naderi, MD, and colleagues provided a review of recent clinical evidence detailing the association of BMI with outcomes in patients with chronic kidney disease, including those with ESRD.

According to the researchers, sophisticated epidemiologic methods that adjusted for confounding have found that the obesity paradox remains robust in ESRD. Further, some hypotheses posit that there may be an association between weight loss and cachexia and adverse outcomes that include cardiomyopathy, arrhythmias, and sudden death. These hypotheses suggest that the survival benefit seen in patients with obesity may be derived from the mechanisms that protect against inefficient energy utilization, cachexia, and protein-energy wasting.

“Given that in ESRD patients, treatment of traditional risk factors has failed to alter outcomes, detailed translational studies of the obesity paradox may help identify innovative pathways that can be targeted to improve survival,” the researchers said.