Counting glomeruli and podocytes: rationale and methodologies.

Abstract

There is currently much interest in the numbers of both glomeruli and podocytes. This interest stems from a greater understanding of the effects of suboptimal fetal events on nephron endowment, the associations between low nephron number and chronic cardiovascular and kidney disease in adults, and the emergence of the podocyte depletion hypothesis. Obtaining accurate and precise estimates of glomerular and podocyte number has proven surprisingly difficult. When whole kidneys or large tissue samples are available, design-based stereological methods are considered gold standard because they are based on principles that negate systematic bias. However, these methods are often tedious and time consuming, and oftentimes inapplicable when dealing with small samples such as biopsies. Therefore, novel methods suitable for small tissue samples, and innovative approaches to facilitate high throughput measurements, such as MRI to estimate glomerular number and flow cytometry to estimate podocyte number, have recently been described. This review describes current gold-standard methods for estimating glomerular and podocyte number, as well as methods developed in the past 3 years. We are now better placed than ever before to accurately and precisely estimate glomerular and podocyte number, and examine relationships between these measurements and kidney health and disease.