Overview of Antibiotic-Induced Nephrotoxicity.

Drug-induced nephrotoxicity accounts for up to 60% of cases of acute kidney injury (AKI) in hospitalized patients and is associated with increased morbidity and mortality in both adults and children. Antibiotics are one of the most common causes of drug-induced nephrotoxicity. Mechanisms of antibiotic-induced nephrotoxicity include glomerular injury, tubular injury or dysfunction, distal tubular obstruction from casts, and acute interstitial nephritis (AIN) mediated by a type IV (delayed-type) hypersensitivity response. Clinical manifestations of antibiotic-induced nephrotoxicity include acute tubular necrosis (ATN), AIN, and Fanconi syndrome. Given the potential nephrotoxic effects of antibiotics on critically ill patients, the use of novel biomarkers can provide information to optimize dosing and duration of treatment and can help prevent nephrotoxicity when traditional markers, such as creatinine, are unreliable. Use of novel kidney specific biomarkers, such as cystatin C and urinary kidney injury molecule-1 (KIM-1), may result in earlier detection of AKI, dose adjustment, or discontinuation of antibiotic and development of nonnephrotoxic antibiotics.

Peritoneal dialysis adequacy: a paradigm shift.

For the past 30 years, nephrologists have focused on a single minimal threshold of Kt/Vurea to determine the adequacy of peritoneal dialysis (PD). To date, there is no evidence that shows Kt/Vurea to be a good surrogate measure of uremic symptom control or nutritional state in patients on PD. Volume of distribution (Vurea) generally is considered equivalent to total body water (TBW). Yet, accurate determination of TBW is difficult. The most recent International Society for Peritoneal Dialysis practice recommendations on prescribing high-quality PD emphasized incorporation of multiple measures rather than the single value of Kt/Vurea. These measures include shared decision-making between the patient and the care team and assessment of health-related quality of life, burden of uremic symptoms, presence of residual kidney function, volume status, and biochemical measures including serum potassium and bicarbonate levels. In some cases, PD prescriptions can be tailored to the patient priorities and goals of care, such as in frail and pediatric patients. Overall, there has been a paradigm shift in providing high-quality care to PD patients. Instead of focusing on small solute clearance in the form of Kt/Vurea, nephrologists are encouraged to use a more comprehensive assessment of the patient as a whole.

Prescribing high-quality peritoneal dialysis: The role of preserving residual kidney function.

Maintenance of residual kidney function (RKF) is independently associated with increased survival in patients with end-stage renal disease. Presence of RKF is also associated with improved volume status, better nutritional status, reduced erythropoietin requirement, and decreased rate of peritonitis in patients on peritoneal dialysis (PD). Thus, the preservation of RKF is an important therapeutic end point in the management of patients on PD. Measurement of RKF in PD patients should be based on the mean of 24-h urinary creatinine and urea clearances, and ideally, this should be done quarterly. Compared to those started on hemodialysis, patients initiated on PD appear to have slower decline in RKF. The choice of PD modality should be based on patient preference, as there is no clear evidence to date showing one modality is superior than the other in preserving RKF. Peritoneal dialysates with neutral pH and low glucose degradation products seem to have a favorable effect on RKF. An angiotensin-converting enzyme inhibitor or angiotensin receptor blocker should be used whenever possible to preserve RKF and reduce cardiac mortality. Both loop diuretics and icodextrin can be utilized to maintain fluid balance in PD patients. However, caution should be taken to avoid volume depletion which could accelerate RKF decline. Short-term use of aminoglycosides does not have a detrimental impact on RKF, but prolonged use (>3 weeks) should be avoided to minimize the risk of ototoxicity. Lastly, potential nephrotoxic agents such as intravenous contrast should be used judiciously.

Treatment of Hyperkalemia With a Low-Dose Insulin Protocol Is Effective and Results in Reduced Hypoglycemia.

INTRODUCTION: Complications associated with insulin treatment for hyperkalemia are serious and common. We hypothesize that, in chronic kidney disease (CKD) and end-stage renal disease (ESRD), giving 5 units instead of 10 units of i.v. regular insulin may reduce the risk of causing hypoglycemia when treating hyperkalemia. METHODS: A retrospective quality improvement study on hyperkalemia management (K+ ≥ 6 mEq/l) from June 2013 through December 2013 was conducted at an urban emergency department center. Electronic medical records were reviewed, and data were extracted on presentation, management of hyperkalemia, incidence and timing of hypoglycemia, and whether treatment was ordered as a protocol through computerized physician order entry (CPOE). We evaluated whether an educational effort to encourage the use of a protocol through CPOE that suggests the use of 5 units might be beneficial for CKD/ESRD patients. A second audit of hyperkalemia management from July 2015 through January 2016 was conducted to assess the effects of intervention on hypoglycemia incidence. RESULTS: Treatments ordered using a protocol for hyperkalemia increased following the educational intervention (58 of 78 patients [74%] vs. 62 of 99 patients [62%]), and the number of CKD/ESRD patients prescribed 5 units of insulin as per protocol increased (30 of 32 patients [93%] vs. 32 of 43 [75%], P = .03). Associated with this, the incidence of hypoglycemia associated with insulin treatment was lower (7 of 63 patients [11%] vs. 22 of 76 patients [28%], P = .03), and there were no cases of severe hypoglycemia compared to the 3 cases before the intervention. CONCLUSION: Education on the use of a protocol for hyperkalemia resulted in a reduction in the number of patients with severe hypoglycemia associated with insulin treatment.

Indication for Dialysis Initiation and Mortality in Patients With Chronic Kidney Failure: A Retrospective Cohort Study.

BACKGROUND: Initiation of maintenance dialysis therapy for patients with chronic kidney failure is a period of high risk for adverse patient outcomes. Whether indications for dialysis therapy initiation are associated with mortality in this population is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 461 patients who initiated dialysis therapy (hemodialysis, 437; peritoneal dialysis, 24) from January 1, 2004, through December 31, 2012, and were treated in facilities operated by a single dialysis organization. Follow-up for the primary outcome was through December 31, 2013. PREDICTOR: Clinically documented primary indication for dialysis therapy initiation, as categorized into 4 groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown. OUTCOMES: All-cause mortality. RESULTS: During a median follow-up of 2.4 years, 183 (40%) patients died. Crude mortality rates were 10.0 (95% CI, 6.8-14.7), 12.7 (95% CI, 10.2-15.7), 21.7 (95% CI, 16.4-28.6), and 12.2 (95% CI, 6.8-14.7) deaths/100 patient-years among patients initiating dialysis therapy primarily for laboratory evidence of kidney function decline, uremic symptoms, volume overload or hypertension, and other/unknown reason, respectively. Following adjustment for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis therapy for uremic symptoms, volume overload or hypertension, or other/unknown reasons was associated with 1.12 (95% CI, 0.72-1.77), 1.69 (95% CI, 1.02-2.80), and 1.28 (95% CI, 0.73-2.26) times higher risk, respectively, for subsequent mortality compared to initiation for laboratory evidence of kidney function decline. LIMITATIONS: Possibility of residual confounding by unmeasured variables; reliance on clinical documentation to ascertain exposure. CONCLUSIONS: Patients initiating dialysis therapy due to volume overload may have increased risk for mortality compared with patients initiating dialysis due to laboratory evidence of kidney function decline. Further studies are needed to identify and test interventions that might reduce this risk.