Q&A An inDEPTH Look at Kidney Week

For a recent PW Podcast, we spoke with two presenters from Kidney Week 2023. First, Jeremy Reiter, MD, PhD, talked about the underpinnings of kidney diseases, as well as the Tabula Sapiens project, to which his lab contributed in-depth transcriptome data from various sites along the nephron. Also, Joseph Vassalotti, MD, discussed how doctors should properly test for renal function and about albuminuria.

Tell us about the Tabula Sapiens project.

Tabula Sapiens was a multi-institutional, highly collaborative project that sought to describe the transcriptomes of many tissues and cell types at a single cell resolution. My part was to isolate cells from human kidneys and then describe the transcriptome. All the genes that were being transcribed were expressed within individual cells within the kidney.

That project describes which genes are expressed in which tissues, and even for fairly rare cell types, which constellations of genes are expressed.

That gives us unprecedented information about the various transcriptional programs that are used by cells throughout the body. We are in the process of using that data to understand what the computer programming, if you will, for many different cell types within the body actually is, as well as the diversity of cell types and their computer programs that they’re running.

The nephrons have a number of cell types that we’ve known something about, but having single-cell transcriptional data helps to elucidate all the possible genes that are being expressed within the glomerular cells, the podocytes, the parietal cells, the proximal tubule cells, the intercalated cells, and the distal collecting duct.

What’s great about a fairly agnostic attempt at describing the cells of a tissue at a single-cell level is that in addition to the tubules, we get all the non-epithelial cells. There are lots of fibroblasts and immune cells, for example, within the kidney, and we can describe those.

Does the kidney’s importance get enough awareness?

There’s a lot to be discovered in kidney health. CKD is a fairly prevalent disease, and as we get better at treating other diseases, it accounts for a growing proportion of deaths. We really have a very poor understanding of the molecular mechanisms that underlie CKD. A challenge for all of us in the biomedical community over the next decade is to discover the etiologies of CKD and maybe some better-targeted therapies that can help to prevent those diseases.

Tell us about the National Kidney Foundation.

As part of Kidney Week, we had World Kidney Day in March, and the theme was kidney health for all, which is intended to transcend some of the challenges faced with kidney health in terms of disasters and epidemics, as well as kidney health equity. We’ve increasingly recognized that social determinants of health impact risk factors for kidney disease, increased prevalence of kidney disease, and less access to patient-centric treatments for kidney failure.

The National Kidney Foundation works on awareness. And one of the key aspects of that is “understand your risk.” Patients can take a kidney risks quiz at minuteforyourkidneys.org.There are also efforts to engage in community interventions to improve kidney health equity and improve awareness and understanding of risk, but also to start to develop, particularly with research and community partnerships, ways of addressing improved access to healthy food, access to clinicians, and trust in clinicians.

What are some problems around albuminuria and the way it’s being recognized?

Albuminuria is the missing test—the missed opportunity. Therefore, patients are under-diagnosed and poorly risk stratified, and some are missed. About 40% of participants in NHANES have kidney disease if they have diabetes, but 11% of that 40% has a normal eGFR (>60) with an albuminuria or increased urine-albumin ratio test. So, you miss 25% of patients with diabetes and CKD if you don’t do the albumin-to-creatinine ratio and only test the eGFR.

The evidence is stronger for interventions like ACE inhibitors and ARBs in the setting of elevated albuminuria. Candidates for SGLT2 inhibitors are determined by the level of albuminuria, and we know these drugs reduce the risk for kidney failure in randomized trials by 30% to 40%, irrespective of whether patients have diabetes.

In other words, albuminuria detects kidney disease and guides intervention. But I think there’s a lot of confusion in the US about the different tests. I think the urine albumin-to-creatinine ratio should be the preferred test. It’s the most sensitive and it’s capable of being standardized.