What is CIN (Contrast-Induced Nephropathy)?

From the Guidelines

In patients with chronic kidney disease undergoing angiography, isosmolar contrast agents are indicated and preferred to minimize the risk of contrast-induced nephropathy. This recommendation is based on the evidence from the 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction 1. The use of isosmolar contrast agents, such as iodixanol, has been shown to lessen the rise in creatinine and reduce the risk of contrast-induced nephropathy compared to low-osmolar contrast media in patients with chronic kidney disease or diabetes mellitus 1. However, more recent studies have suggested that the risk of contrast-induced nephropathy cannot be attributed to osmolarity alone, and that ionicity and other characteristics of specific agents may also play a role 1. Despite this, the preference for isosmolar contrast agents remains, particularly in patients with chronic kidney disease or diabetes mellitus undergoing angiography. It is essential to identify patients with chronic kidney disease and adjust the dose of renally cleared cardiovascular drugs, such as antiplatelet and antithrombin agents, to minimize the risk of bleeding complications and optimize care for this high-risk population 1. Key considerations in the management of patients with chronic kidney disease include:

• Screening for kidney disease by estimating glomerular filtration rate, testing for microalbuminuria, and measuring the albumin-to-creatinine ratio 1
• Adjusting the dose of renally cleared drugs based on estimated creatinine clearance using the Cockroft-Gault formula 1
• Minimizing the risk of contrast-induced nephropathy by using isosmolar contrast agents and optimizing hydration protocols 1

From the Research

Cinacalcet Treatment

• Cinacalcet has been proven to be a reasonable alternative for several patient subgroups with primary hyperparathyroidism, controlling hypercalcemia and hypophosphatemia sufficiently 2.
• The medication lowers PTH levels and improves cognitive parameters, with a normalization rate of serum Ca levels reported at 90% (CI: 0.82 to 0.96) 3.
• Cinacalcet reduces serum calcium levels, with the higher the baseline Ca levels, the greater Ca reduction with cinacalcet treatment 3.
• The results from meta-analyses support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with primary hyperparathyroidism 3, 4.

Efficacy and Safety

• Cinacalcet was found to be effective in reducing serum calcium in patients with primary hyperparathyroidism, with a decrease in serum calcium by at least 1 mg/dl in all patients and normalization in 10 5.
• PTH levels decreased by 17.1% compared to baseline, although never reaching a normal value 5.
• The medication is safe with tolerable side effects, and no significant difference in overall adverse events was noted compared to placebo 4.
• The pooled weighted adverse event rate was 45% (95% CI 32 to 59%) in non-randomized studies 4.

Comparison to Other Treatments

• Parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, but medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups 2.
• Cinacalcet may be considered as a first choice in patients with hyperplasia in all glands rather than an isolated adenoma, patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms 2.

CIN Diagnosis

• A broad-based approach using in situ hybridization and immunohistochemistry can help differentiate CIN from its mimics, with the utility of detecting HPV DNA or the L1 capsid protein 6.
• The use of a panel of biomarkers, including p16, Ki67, importin-β, exportin-5, and Mcl1, can also aid in the diagnosis of CIN 6.
• Incorrect diagnoses of CIN 1-2 can be prevented with the use of in situ detection of viral DNA/capsid protein or immunohistochemistry detection of biomarkers 6.