KPMP Clinical-Pathological-Molecular correlation publications

KPMP Clinical-Pathological-Molecular correlation publications

May 19, 2022

The KPMP Clinical-Pathological-Molecular correlation (CPMC) serves to coordinate and identify compelling individual cases that highlight the advances of KPMP to clinically focused communities. Writing groups are organized to write these cases and include representatives from the clinical, pathology, and tissue interrogation KPMP sites. The clinical component of the CPMC provides a thorough summary of the patient case, the pathology component introduces findings that agree and/or do not agree with the clinical assessments made pre-and post-biopsy, while the tissue interrogation component illustrates the molecular methodology of each case. All three components work together to provide insights and develop a scientific theme for each patient case.  Each case has a patient representative who offers a unique perspective to highlight the case’s important and novel concepts. Scientific advancements of KPMP are motivated by the feedback of our KPMP participants.

Our first two published CPMCs and discussion from the authors are noted below.

Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney Disease, published in CJASN

When asked about the uniqueness of the KPMP CPMC process, Dr. Michael Eadon (Indiana University) notes “Classic clinicopathologic correlations (without the molecular component) have long held educational utility, seeking to understand the causes of a patient’s disease and generate hypotheses from these observations. A CPMC case adds a layer of novel molecular data to enhance our interpretation and draw out subtle findings which may not have been appreciated in the clinical and pathology assessment.”

One highlight of the KPMP CPMC process is that each case includes a patient perspective. Jack Bebiak, a KPMP patient partner from Indiana University, describes in his CPMC “The patient members of the KPMP consortium are thrilled by this study as an example of how a molecular atlas might advance the prevention, early detection and specific care for individuals with chronic kidney conditions. Specifically, this abstract is a vanguard of the patient-driven clinical care advancements from the Kidney Precision Medicine Project, fostering the collaboration between physician and patient, and resulting in improved health outcomes and quality of life. This CPMC case study, through physician-patient knowledge and transparency, illustrates how integration of novel molecular methodology with clinical information may ultimately help practitioners diagnose and treat kidney disease and help patients with disease prevention, understanding, and motivation for self-accountability of hypertension and comorbidity management.”

First author Dr. Jiten Patel (UT Southwestern) described his experience in the KPMP CPMC process as "The standard kidney biopsy is sometimes not congruent with our clinical picture. This case was able to show that there is more than meets the eye with a routine kidney biopsy. While the results we illustrated with the molecular analysis were reassuring that our clinical suspicions are correct, it also showed that we still have more to learn. This experience was enjoyable as it was a truly collaborative effort with the clinician, pathologist, basic scientist, and patient, illustrating that integrative medicine is possible."  

Integrated single-cell sequencing and histopathological analyses reveal diverse injury and repair responses in a participant with acute kidney injury: a clinical-molecular-pathologic correlation, published in Kidney International.

Dr. Rajasree Menon (University of Michigan) describes the importance of the study: “As a researcher, I am motivated by the findings from this integrated study.  The molecular and cellular profiles revealed a dynamic and active AKI phenotype consistent with the histopathological heterogeneity observed and provide insights into AKI mechanisms of successful versus unsuccessful repair not typically obtained from routine clinical and pathologic diagnostic workup. This knowledge has the potential to direct molecular therapy to boost reparative states and inhibit further damage.”

Dr. Charles Alpers (University of Washington) is a member of the KPMP CPMC working group, the group who organizes the CPMC process. He notes “Pathologists who interpret renal biopsies typically utilize an armamentarium of sophisticated technologies to identify structural changes within kidney tissues that include light microscopy, ultrastructural study by electron microscopy, and immunofluorescence microscopy. These technologies have been developed and refined over many decades, and their application has served as the basis for identification of the defining diagnostic features of most renal diseases. The CPMC cases dramatically illustrate the limitations of current renal pathology diagnostic practice by revealing that there is considerable diagnostic information that is not extracted by the standard pathology assessments which remains embedded within the renal tissue. The additional application of recently developed molecular approaches, previously limited to basic research settings but now applied to renal biopsies within the KPMP, and integration of the new findings with standard renal pathology assessments, has extracted previously unknown types of information that enabled more exact diagnoses and offers the potential for better matching of patients with therapeutic regimens directed towards their underlying disease processes.”

We have several CPMCs planned in the next phase of KPMP and hope they will be of value to the clinical and research community.