Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?

Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and using prophylactic antimicrobial medications. Graft survival depends on factors beyond human leukocyte antigen matching such as the level of immunosuppression, infections, and management of other comorbidities. Risk stratification of transplant patients based on predisposing genetic modifiers and applying precision pharmacotherapy may help improving the transplant outcomes. Unlike certain fields such as oncology in which consistent attempts are being carried out to move away from the "error and trial approach," transplant medicine is lagging behind in implementing personalized immunosuppressive therapy. The need for maintaining a precarious balance between underimmunosuppression and overimmunosuppression coupled with adverse effects of medications calls for a gene-based guidance for precision pharmacotherapy in transplantation. Technologic advances in molecular genetics have led to increased accessibility of genetic tests at a reduced cost and have set the stage for widespread use of gene-based therapies in clinical care. Evidence-based guidelines available for precision pharmacotherapy have been proposed, including guidelines from Clinical Pharmacogenetics Implementation Consortium, the Pharmacogenomics Knowledge Base National Institute of General Medical Sciences of the National Institutes of Health, and the US Food and Drug Administration. In this review, we discuss the implications of pharmacogenetics and potential role for genetic variants-based risk stratification in kidney transplantation. A single score that provides overall genetic risk, a polygenic risk score, can be achieved by combining of allograft rejection/loss-associated variants carried by an individual and integrated into practice after clinical validation.

Recurrence of Acute Page Kidney in a Renal Transplant Allograft.

Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

HLA-G dimers in the prolongation of kidney allograft survival.

Human leukocyte antigen-G (HLA-G) contributes to acceptance of allografts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA-G and its specific receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulfide-linked dimeric complexes with high preferential binding and functional activities. Limited data are available on the role of soluble HLA-G dimers in clinical pathological conditions. We describe here the presence of soluble HLA-G dimers in kidney transplant patients. Our study showed that a high level of HLA-G dimers in plasma and increased expression of the membrane-bound form of HLA-G on monocytes are associated with prolongation of kidney allograft survival. We also determined that the presence of soluble HLA-G dimers links to the lower levels of proinflammatory cytokines, suggesting a potential role of HLA-G dimers in controlling the accompanying inflammatory state.

Effect of clinical pharmacy services on the blood pressure of African-American renal transplant patients.

OBJECTIVE: The objective of this study was to determine if African-American renal transplant patients who received direct patient care from a clinical pharmacist had better blood pressure control compared to African-American renal transplant patients who did not have clinical pharmacy services. METHODS: Renal transplant patients were prospectively randomized into an intervention group or a control group. Patients in the intervention group received clinical pharmacy services that included a clinical pharmacist performing patient medication reviews, with emphasis on preventing or resolving medication-related problems and providing medication recommendations. Patients in the control group received routine clinic services, but had no clinical pharmacist interaction. Analysis was performed to detect differences between the intervention and control groups in baseline and quarterly systolic blood pressure (SBP) and diastolic blood pressure (DBP) for one year post-study enrollment. RESULTS: There were no differences between the intervention (N = 13) and control (N = 10) groups in baseline blood pressures or in the percentage of hypertensive patients. Significant differences in the change in SBP and DBP from baseline between the intervention and control groups were observed at the second, third, and fourth quarters of the study, favoring the intervention group (P < .01). Mean SBP was significantly lower in the intervention group at the second (137.8 +/- 15.0 vs 168.9 +/- 15.3), third (135.9 +/- 11.7 vs 164.6 +/- 20.1), and fourth (145.3 +/- 16.8 vs 175.8 +/- 33.9) quarters of the study (P < .05). Mean DBP was significantly lower in the intervention group at the second (76.0 +/- 11.8 vs 84.9 +/- 6.1) and fourth (77.0 +/- 10.2 vs 91.8 +/- 12.0) quarters (P < .05). CONCLUSION: Direct patient care services provided by a clinical pharmacist, in addition to routine clinical services, have a positive effect on the blood pressure of African-American renal transplant patients. A multidisciplinary team that includes a clinical pharmacist is beneficial to patient care.