Fever of Unknown Origin and Cancer

A 62-year-old woman presents to the hospital with an almost 2-year history of intermittent fevers of up to 102°F. She reports that over that same time span, she has become progressively weak and has been experiencing darker urine. The family states that occasionally she is “not acting herself”, but they attribute it to old age. The patient is admitted to the hospital with acute kidney injury (AKI), elevated liver function tests (LFTs), and failure to thrive (FTT), presumably due to her decreased oral intake and poor diet. 
During her hospitalization, she continues to spike fevers up to 103°F, and she becomes increasingly altered to the point where she is minimally responsive. Blood cultures remain negative and a CT of her head shows no acute changes or intracranial bleed. Endocarditis, abscesses, and connective tissue diseases are all ruled out as potential causes of her fever. 
At this point, the patient can be described as having a fever of unknown origin (FUO). By definition, FUO is characterized by a temperature >100.9°F on multiple occasions for at least 3 weeks in addition to a negative workup in a hospital for at least one week. The differential diagnosis of FUO is extensive, although one important diagnosis includes cancer. 
Although the data varies between studies, up to 10% of all FUO cases can be attributed to an underlying cancer. The most likely cancers to present with FUO include the hematological malignancies such as lymphoma, leukemia, multiple myeloma, and myelodysplastic syndrome. Additional solid organ tumors that have been associated with FUO include hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The textbook triad of findings in RCC includes hematuria, flank pain, and a palpable abdominal mass, although these occur in less than 10% of all RCC patients. A persistent fever in combination with some of these findings could lead to further investigation into RCC. Metastases to the liver, especially those of adenocarcinoma origin, have also been implicated in FUO.
Depending on the patient presentation, history, and physical, the workup could vary. Further laboratory studies in addition to basic bloodwork include ESR, CRP, tumor markers, chromosomal studies, and bone marrow biopsies. Potentially helpful imaging studies include an abdominal ultrasound; CT of the chest, abdomen, and pelvis; and PET scans. All of these tests are not necessary in every patient with a diagnosis of FUO. Sound clinical judgment is necessary in order to evaluate which tests are the most beneficial to the patient and which will directly impact clinical decision making.

by
Dr.Akshaya Srikanth
Pharm.D, India

Risks of Hypoglycemic Drugs in Diabetics with CKD

According to the World Diabetic Association (WBA), approximately 40% of adults with diabetes have some degree of chronic kidney disease (CKD). That's a lot of patients more than one might think.They should be getting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker(ARB) for renoprotection, and blood pressure and lipids should be aggressively managed, but how does our approach to managing their antidiabetic therapy change?

We might consider taking a more aggressive approach to their glycemic control. In some clinical trial reports, tight glycemic control has been shown to be the primary determinant of decreased microvascular complications. However, once we've decided how aggressively to manage glycemia, the choice of which antidiabetic to use and is especially important in these patients. Unfortunately, when the therapeutic strategy is to maximize glycemic control, the risk of hypoglycemia also increases - in both frequency and severity. Patients taking oral antidiabetics that are primarily eliminated by the kidneys are particularly susceptible. Furthermore, it should be noted that older patients are also at higher risk. 

Dosing errors are common in CKD patients and can cause poor outcomes. Drugs cleared renally should be dose-adjusted based on creatinine clearance or estimated glomerular filtration rate (eGFR). Dose reductions, lengthening of the dosing interval, or both may be required. 

As metformin is nearly 100% renally excreted, it is contraindicated in a number of patients: when serum creatinine is higher than 1.5 mg/dL in men or 1.4 mg/dL in women, in patients older than 80 years, or in patients with chronic heart failure. The primary concern here is that other hypoxic conditions (e.g., acute myocardial infarction, severe infection, respiratory disease, liver disease) may increase the risk of lactic acidosis. Because of this danger, and despite the fact that metformin is usually the recommended first-line treatment for type 2 diabetes, one should use caution when considering metformin in patients with renal impairment. Similarly, sulfonylureas should be used with care in diabetics with CKD. The clearance of both sulfonylureas and their metabolites is highly dependent on kidney function. As such, severe and sustained episodes of hypoglycemia due to sulfonylurea use have been described in dialysis patients. 

Regardless of which antidiabetic agent is selected, HbA1c and kidney function should be regularly monitored and the antidiabetic regimen appropriately adjusted. As patients with type 2 diabetes tend to progress over time, most will require a combination of agents to achieve desired glycemic control. These combinations should be chosen carefully in patients with CKD.

Finally, awareness of and screening for renal impairment in diabetics is a necessary precursor to successful intervention. In these patients, CKD is underdiagnosed and undertreated, and awareness of the disease is low among providers and patients alike. Early detection of disease via eGFR or urinary albumin excretion can lead to timely, evidence-based intervention and help prevent or delay progression of CKD. Check with the benefits in Improved kidney and cardiovascular outcomes, prevent emergencies, improving quality of life and lower associated costs.

by

Dr.Akshaya Srikanth

Pharm.D