ABSTRACT
Reduced T3 and free T4, elevated thyroid stimulating hormone, and hyporesponsiveness to thyrotropin releasing hormone raise questions about the presence of hypothyroidism in chronic kidney disease (CKD) and raise the possibility of benefit from thyroxine supplementation. A prospective cohort study was conducted on 73 nondiabetic CKD cases. Hypothyroid patients were started on levothyroxine and were reviewed after 3 and 6 months. The mean age of study population was 42.3 ± 16.8 years. Of the total population, 32 (43.8%) cases had hypothyroidism, among whom 2 (2.7%) had overt hypothyroidism and 30 (41.1%) had subclinical hypothyroidism. Prevalence of hypothyroidism increased with increasing severity of CKD. There were 1 (3.1%) case with hypothyroidism in stage 3b, 8 (25%) cases in stage 4, and 23 (71.9%) cases in stage 5. The mean estimated glomerular filtration rate (ml/min/1.73 m2) at baseline was 13.7 ± 8.9 which increased to 17.5 ± 6.8 and 22.4 ± 9.3 after 3 and 6 months of thyroid hormone replacement therapy (THRT), respectively (P < 0.001). Hypothyroidism is commonly associated with nondiabetic CKD and its prevalence increases with declining renal function. THRT significantly improves renal function in nondiabetic CKD with hypothyroidism.
ABSTRACT
Protein X-ray structures are determined with ionizing radiation that damages the protein at high X-ray doses. As a result, diffraction patterns deteriorate with the increased absorbed dose. Several strategies such as sample freezing or scavenging of X-ray-generated free radicals are currently employed to minimize this damage. However, little is known about how the absorbed X-ray dose affects time-resolved Laue data collected at physiological temperatures where the protein is fully functional in the crystal, and how the kinetic analysis of such data depends on the absorbed dose. Here, direct evidence for the impact of radiation damage on the function of a protein is presented using time-resolved macromolecular crystallography. The effect of radiation damage on the kinetic analysis of time-resolved X-ray data is also explored.
