No abstract

Targeted protein degradation is a powerful tool in determining the function of specific proteins or protein complexes. We fused nanobodies to SPOP, an adaptor protein of the Cullin-RING E3 ubiquitin ligase complex, resulting in rapid ubiquitination and subsequent proteasome-dependent degradation of specific nuclear proteins in mammalian cells and zebrafish embryos. This approach is easily modifiable, as substrate specificity is conferred by an antibody domain that can be adapted to target virtually any protein.

Background: Several registries and centers have reported the results of renal biopsies from different parts of the world. As there are few data regarding the epidemiology of glomerulonephritis (GN) in South Korea, we conducted this study on renal biopsy findings during the last 20 years from a single center.Methods: Data for 818 patients who underwent renal biopsy at our center between 1992 and 2011 were collected retrospectively. All kidney specimens were examined with light microscopy (LM) and immunofluorescent microscopy (IF).Results: There were 818 cases of native kidney biopsies. In cases of primary GN, the most frequent type of renal pathology in adults (18–59 years) was mesangial proliferative GN (MsPGN, 34.5%) followed by IgA nephropathy (IgAN, 33.3%) and membranous GN (MGN, 8.8%). Indications in adults (18–59 years) were asymptomatic urinary abnormalities (75.3%) followed by nephrotic syndrome (19.8%) and acute kidney injury (AKI, 3.4%).Conclusions: Among 818 renal biopsy specimens, MsPGN and IgAN were the most frequent biopsy-proven renal diseases. MGN was the third most common cause of primary GN and lupus nephritis (LN) was the most common secondary glomerular disease. Our data contribute to the epidemiology of renal disease in South Korea.

SummaryThyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves’ disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient’s dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment.Learning points:The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

BackgroundThe purpose of this study was to assess the role of hypophosphatemia in major clinical outcomes of patients treated with low- or high-intensity continuous renal replacement therapy (CRRT).MethodsWe performed a retrospective analysis of data collected from 492 patients. We divided patients into two CRRT groups based on treatment intensity (greater than or equal to or less than 40 mL/kg/hour of effluent generation) and measured serum phosphate level daily during CRRT.ResultsWe obtained a total of 1,440 phosphate measurements on days 0, 1, and 2 and identified 39 patients (7.9%), 74 patients (15.0%), and 114 patients (23.1%) with hypophosphatemia on each of these respective days. In patients treated with low-intensity CRRT, there were 23 episodes of hypophosphatemia/1,000 patient days, compared with 83 episodes/1,000 patient days in patients who received high-intensity CRRT (P < 0.01). Multiple Cox proportional hazards analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) III score, utilization of vasoactive drugs, and arterial pH on the second day of CRRT were significant predictors of mortality, while serum phosphate level was not a significant contributor to mortality.ConclusionAPACHE score, use of vasoactive drugs, and arterial pH on the second CRRT day were identified as significant predictors of mortality. Hypophosphatemia might not be a major risk factor of increased mortality in patients treated with CRRT.

No abstract

Background/Aims: Aldosterone antagonists have been proven to be efficient in the management of hypertension and the reduction of proteinuria; however, they are not widely used because of the risk of hyperkalemia. We assessed the predictors of hyperkalemia risk following hypertension control using aldosterone blockade in the presence or absence of chronic kidney disease (CKD). Methods: A total of 6,575 patients with hypertension treated between January 1, 2000, and November 30, 2012, were evaluated for the safety of an aldosterone-blocking agent (spironolactone) added to preexisting blood pressure-lowering regimens. Hyperkalemia was defined as a serum potassium level ≥5.0 mEq/l. All patients used 3 mechanistically complementary antihypertensive agents, including a diuretic and a RAAS blocker. Patients were evaluated after 4 and 8 weeks of treatment. The incidence of hyperkalemia, significant renal dysfunction [a reduction of the estimated glomerular filtration rate (eGFR) ≥30%], and adverse effects was assessed. Results: The incidence of hyperkalemia in the presence or absence of CKD was 50.4 and 42.6% after 4 weeks (p = 0.001) and 3.8 and 3.0% after 8 weeks, respectively (p = 0.371). A logistic regression analysis revealed that medication, CKD, basal hyperkalemia, reduction in eGFR, and diabetes were all predictive of a hyperkalemia risk following spironolactone use. Conclusion: Spironolactone was well tolerated by selected CKD patients. The risk of serious hyperkalemia or a significant reduction of eGFR appears to be low. Strict monitoring over the first month of treatment followed by standard surveillance for angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers is suggested.

No abstract