The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three‐dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity.
Background
Both early recognition of glomerular injury and diagnosis of renal injury remain important problems in clinical settings, and current diagnostic biomarkers have limitations. The aim of this review was to determine the diagnostic accuracy of urinary nephrin for detecting early glomerular injury.
Methods
A search was conducted through electronic databases for all relevant studies published until January 31, 2022. The methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled sensitivity, specificity, and other estimates of diagnostic accuracy were determined using a random effect model. The Summary Receiver Operating Characteristics (SROC) was used to pool the data and to estimate the area under the curve (AUC).
Results
The meta-analysis included 15 studies involving 1587 participants. Overall, the pooled sensitivity of urinary nephrin for detecting glomerular injury was 0.86 (95% CI 0.83–0.89) and specificity was 0.73 (95% CI 0.70–0.76). The AUC-SROC to summarise the diagnostic accuracy was 0.90. As a predictor of preeclampsia, urinary nephrin showed a sensitivity of 0.78 (95% CI 0.71–0.84) and specificity of 0.79 (95% CI 0.75–0.82), and as a predictor of nephropathy the sensitivity was 0.90 (95% CI 0.87–0.93), and specificity was 0.62 (95% CI 0.56–0.67). A subgroup analysis using ELISA as a method of diagnosis showed a sensitivity of 0.89 (95% CI 0.86–0.92), and a specificity of 0.72 (95% CI 0.69–0.75).
Conclusion
Urinary nephrin may be a promising marker for the detection of early glomerular injury. ELISA assays appear to provide reasonable sensitivity and specificity. Once translated into clinical practice, urinary nephrin could provide an important addition to a panel of novel markers to help in the detection of acute and chronic renal injury.
Graphical abstract
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