Sui Phin Kon

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell–related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group—namely, the tolerant recipients—were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS‐independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross‐validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Rapid development of renal failure secondary to AA-type amyloidosis in a patient with polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a common chronic inflammatory disorder affecting patients over the age of 50. Renal involvement in PMR is extremely rare and very few cases of AA amyloidosis secondary to PMR have been described in literature. We present a case of a patient with history PMR who developed nephrotic range proteinuria and rapidly deteriorating renal function secondary to AA amyloidosis within 18 months of the onset of symptoms of PMR. This case reinforces the association of PMR with secondary AA amyloidosis and highlights the importance of monitoring renal function in patients with PMR.

Cardiorenal syndrome: review of our current understanding

Renal and cardiac diseases are both prevalent and carry significant morbidity and mortality. They share common vascular risk factors and are physiologically interlinked. Dysfunction in one organ affects the other. Concurrent renal and cardiac disease is associated with a poor prognosis. This close relationship is reflected through cardiorenal syndrome. A classification system has been proposed; however, the underlying process is complex and multifactorial. Management of this syndrome focuses on improving heart function, reducing volume overload, and managing heart failure and chronic kidney disease. This, however, is challenging, limited by paucity of evidence and may lead to suboptimal therapy. Increased recognition of this syndrome should raise awareness in providing early therapy and avoiding adverse outcomes due to under-treatment. In this article, we provide an overview of our current understanding of cardiorenal syndrome, as well as its pathophysiology and treatment options.

NEPHROTIC AND ANTI‐PHOSPHOLIPID SYNDROMES: MULTISYSTEM CONDITIONS ASSOCIATED WITH ACUTE MYOCARDIAL INFARCTION IN YOUNG PATIENTS

SUMMARY Acute myocardial infarction is relatively uncommon in patients under the age of 40 years. Unlike the older patients where rupture of coronary artery atherosclerotic plaque is the main underlying pathology, the pathogenesis in younger patients can be varied and may require different diagnostic and therapeutic approaches. Hypercoagulable state associated with nephrotic syndrome and antiphospholipid syndrome can lead to the development of occlusive coronary artery thrombus in absence of atherosclerotic coronary artery disease. Acute myocardial infarction in such a setting can sometimes be the first manifestation of an underlying disease. We describe a case of myocardial infarction in a young man with both nephrotic and antiphospho-lipid syndromes and present a brief literature review.Acute myocardial infarction is relatively uncommon in patients under the age of 40 years. Unlike the older patients where rupture of coronary artery atherosclerotic plaque is the main underlying pathology, the pathogenesis in younger patients can be varied and may require different diagnostic and therapeutic approaches. Hypercoagulable state associated with nephrotic syndrome and antiphospholipid syndrome can lead to the development of occlusive coronary artery thrombus in absence of atherosclerotic coronary artery disease. Acute myocardial infarction in such a setting can sometimes be the first manifestation of an underlying disease. We describe a case of myocardial infarction in a young man with both nephrotic and antiphospho-lipid syndromes and present a brief literature review.