Reducing the risk of denosumab-induced hypocalcemia in patients with advanced chronic kidney disease: a quality improvement initiative.

Denosumab can improve bone health in advanced kidney disease (CKD) but is associated with hypocalcemia. We created a clinical care pathway focused on the safe provision of denosumab in advanced CKD that reduced the risk of hypocalcemia by 37% at our hospital. Similar pathways could be adopted and tested in other centers. PURPOSE: There is an increased risk of hypocalcemia with denosumab in advanced chronic kidney disease (CKD). We aimed to reduce the proportion of patients with advanced CKD who experienced denosumab-induced hypocalcemia at our center. METHODS: We conducted a quality improvement (QI) project of patients with CKD stage 3b or less (i.e., estimated glomerular filtration rate <45 mL/min/1.73m2 including dialysis) who were part of the Osteoporosis and Bone Disease Program at St. Joseph's Health Care London (Canada) between December 2020 and January 2023. Our intervention was a clinical care pathway which optimized CKD mineral and bone disorder (CKD-MBD) and 25-hydroxyvitamin levels; provided calcium and vitamin D prophylaxis; promoted multidisciplinary communication between bone and kidney specialists; and carefully monitored calcium post-denosumab injection. Our primary outcome measure was the proportion of patients with hypocalcemia (defined by albumin-corrected serum calcium <1.9mmol/L) at 60 days. Process measures included the appropriate provision of calcium and vitamin D prophylaxis. Balance measures included the development of hypercalcemia and hyperphosphatemia following prophylaxis. We used plan-do-see-act cycles to study four tests of change and presented results using descriptive statistics and run charts. RESULTS: There were 6 patients with advanced CKD treated with denosumab prior to the implementation of our care pathway (March 2015-October 2020; 83% receiving dialysis). At the time of their denosumab injection, 83% were using 500-1000 mg of calcium, and 83% used 1000-2000 IU of vitamin D3. Fifty percent developed denosumab-induced hypocalcemia. Following the implementation of our care pathway, 15 patients (40% receiving dialysis) were treated with denosumab. Ninety-three percent received calcium at a daily dose of 350 to 2250 mg and 87% received 1000-2000 IU of vitamin D3. Thirteen percent developed denosumab-induced hypocalcemia. There was no hypercalcemia or hyperphosphatemia. CONCLUSIONS: A clinical care pathway focused on the safe provision of denosumab in advanced CKD reduced the risk of hypocalcemia in patients treated in our hospital. Similar pathways could be adopted and tested in other centers.

Medication reconciliation in hemodialysis patients.

Medication reconciliation is an effective process to reduce adverse drug events (ADEs) and harm associated with the loss of medication information as patients transfer between health care settings. Patients with end stage renal disease (ESRD) are at a high risk of experiencing drug-related problems (DRPs) because they take many medications, have multiple comorbidities, and require frequent medication changes. We evaluated the potential impact of medication reconciliation and optimization in the ambulatory care setting at the time of patient transfer from an in-centre dialysis unit to a satellite dialysis unit. Overall, 15 patients (78.8%) had at least one unintended medication variance. The majority of unintended variances (56%) were caused by the physician/nurse practitioner (NP) omitting an order for medication that the patient was taking. In this small study, medication reconciliation was effective at identifying and rectifying medication errors and optimizing pharmacotherapy at the time of transfer from an in-centre hemodialysis to a satellite dialysis unit.

Effectiveness of furosemide in patients on peritoneal dialysis.

BACKGROUND: Residual renal function (RRF) is a marker for a good index of health and is associated with improved survival for individuals with end stage renal disease on peritoneal dialysis. As RRF declines with time on dialysis, fluid balance is more difficult to achieve. Urine output plays a vital role in fluid removal and it has been postulated that loop diuretics improve diuresis in peritoneal dialysis (PD) patients. The aim of this study is to evaluate our use of furosemide and its effect on diuresis in a home peritoneal dialysis program. METHODS: Sixty-one patients met inclusion criteria of having been on PD continuously for one year from their start date with complete 24-hour urine kinetics. Twenty patients were on furosemide and 41 patients were in the control group. Data for urine volume (UV), serum creatinine (SCr), total and residual creatinine clearance (CrCl(total) and CrCl(residual)), total and residual urea clearance (Kt/V(total) and Kt/V(residual)) and dry body weight were collected at baseline, six months and one year. The average change in UV CrCl(total), and Kt/V(total) from baseline at six and 12 months and the proportion of patients who developed anuria at one year were determined. RESULTS: UV declined in the furosemide and control groups at six months by an average of 78.00 +/- 445.2 mL/day and 105.5 +/- 401.8 mL/day (p=0.8) and at 12 months by 85.00 +/- 481.7 mL/day and 110.7 +/- 455.4 mL/day (p=0.8), respectively. CrCl declined in the furosemide and control groups at six months by an average of 5.55 +/- 20.4 mL/min and 4.52 +/- 29.0 mL (p=0.9), and at 12 months by 3.95 +/- 35.5 mL/min and 9.05 +/- 28.4 mL/min (p = 0.5) respectively. Kt/V increased by 0.0850 +/- 0.890 in the furosemide group and declined by 0.0456 +/- 0.614 in the control group at six months (p=0.5), but after 12 months, Kt/V declined in both the furosemide and control groups by 0.00400 +/- 0.565 and 0.162 +/- 0.558 (p=0.5) respectively. Only one patient (five per cent) in the furosemide group developed anuria after one year on PD, whereas nine patients (22%) in the control group became anuric (p=0.1). CONCLUSION: Furosemide did not have a statistically significant effect in either improving UV or preserving RRF in patients on PD for one year, but this study was not adequately powered to show an association. Although not statistically significant, fewer patients were anuric at one year in the furosemide group (five per cent versus 22%). Furosemide was not shown to be detrimental to either RRF or UV.

Laboratory assessment of kidney function.

It is important to be able to accurately predict the function of the kidneys by estimating GFR. GFR is a strong predictor for the onset and complications of CKD and it also allows us to dose-adjust medications. It, unfortunately, cannot be measured directly, so we have to depend on surrogate markers such as creatinine to estimate it. With the development of newer predictive equations such as the MDRD equations, we can more accurately estimate GFR in certain populations.

An update on the treatment and management of stroke.

There have been huge advancements in the prophylaxis and treatment of stroke. The majority of patients who have a stroke are asymptomatic prior to the event. This makes it extremely important to identify high-risk patients and administer prophylaxis where appropriate. However, risk factors, prophylaxis and treatment strategies are less clear in dialysis patients due to the lack of studies. Patients with chronic kidney disease have a higher risk of experiencing a stroke and dying from it. More studies need to be done in this area. For now, modifiable risk factors such as blood pressure and nutrition, should be promoted and prophylaxis and treatment administered with extra vigilance due to these patients' increased bleeding risk.

An update on the treatment and management of diabetic peripheral neuropathy.

It is clear that the majority of the evidence for symptomatic management of DPN is for either TCAs or anticonvulsants. The Canadian Diabetes Association recommends agents from these classes as first-line therapy. Though these agents appear to be effective, the management of neuropathic pain is still quite difficult and many patients only achieve partial relief from therapy while others find no relief. It is important to focus on the prevention of onset and progression of diabetic neuropathy by dealing with the root of the problem, glycemic control. Patients should be educated on the importance of intensive glycemic control for the prevention of all diabetes complications, including peripheral neuropathy (Bril & Perkins, 2003).

A review of hypertension management in Canada.

Reducing a patient's global CV risk requires a multifactorial approach. Medication is only a part of a patient's therapy. Lifestyle modifications such as diet and exercise should be encouraged. Several larger trials in hypertension have provided us with new recommendations: Statins for hypertensive patients regardless of cholesterol. ASA in patients with well-controlled hypertension. Thiazide diuretics and ARBs can be initial treatment options. Avoid the following as initial monotherapy in hypertensive patients: beta-blockers in the elderly, ACE inhibitors in black patients and alpha-adrenergic blockers. Follow-up of these largely asymptomatic patients should be performed frequently. Reasons for poor response should be investigated and additional antihypertensive therapy added, if appropriate, to achieve target blood pressures.

Diabetes mellitus Canadian clinical practice guidelines update.

Data from the National Diabetes Surveillance Strategy (NDSS) found the prevalence of physician-diagnosed diabetes in adults to be 4.8% (Health Canada Database, 2002). Population-based studies have found the prevalence rates to be much higher. The Canadian Diabetes Association has developed new clinical practice guidelines. In this article, I will attempt to highlight some of the major changes from the previously published guidelines.

Potential drug interaction between simvastatin and danazol causing rhabdomyolysis.

Rhabdomyolysis is a life-threatening clinical and biochemical syndrome that results from injury to skeletal muscle. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been associated with myopathy and rhabdomyolysis. Although rhabdomyolysis is a rare adverse event associated with this class of drugs, their prevalent use in the management of dyslipidemia makes it increasingly important for clinicians to understand the nature of this condition. Rhabdomyolysis can occur with all statins when used alone and particularly when combined with other drugs that are themselves myotoxic or that elevate the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral bioavailability. In this report, we describe a case of rhabdomyolysis and acute renal failure secondary to the interaction between danazol and simvastatin.