Diagnosing and Managing Kidney Disease

Renal disease diagnostics and management has been revolutionised by advancements in biomarkers, microscopy, and imaging techniques. Traditional biomarkers such as serum creatinine and blood urea nitrogen (BUN) have long served as the cornerstone for evaluating kidney function. However, the discovery of novel biomarkers like cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) has significantly enhanced our ability to detect and understand renal injury at earlier stages. These biomarkers provide insights into the molecular and cellular mechanisms underlying kidney disease, enabling more precise and timely interventions.

Microscopy has also seen remarkable progress, with techniques such as electron microscopy, immunohistochemistry, and more recently, Fourier Ptychographic Microscopy (FP). FP, in particular, offers high-resolution, wide-field imaging without the need for staining, allowing for detailed examination of renal tissue architecture and pathology. This innovation facilitates the identification of subtle histological changes that might be missed with conventional microscopy, thus improving diagnostic accuracy and understanding of disease mechanisms.

Imaging technologies have similarly evolved, with enhancements in ultrasound, CT, and MRI being complemented by advanced techniques like contrast-enhanced ultrasound and functional MRI (fMRI). These methods not only provide detailed anatomical images but also offer functional insights into renal perfusion, filtration, and metabolic activity. The integration of these advanced imaging modalities with novel biomarkers and microscopy techniques has significantly improved the diagnosis, risk stratification, and management of kidney disease, paving the way for personalised treatment approaches and better patient outcomes. These advancements underscore a new era in nephrology, marked by precision medicine and comprehensive patient care.

Recent key publications

1) Patient-Centered Quality Measures for Dialysis Care: A Report of a Kidney Disease Outcomes Quality Initiative (KDOQI) Scientific Workshop Sponsored by the National Kidney Foundation. Am J Kidney Dis 2024; 83:636-647. Weiner DE, Delgado C, Flythe JE et al. Link to full article

The authors of this article present a report of a workshop that focused on renal disease and outcome quality parameters. The report presents a comprehensive analysis of the current quality measures in dialysis care, emphasising the need for patient-centred approaches. The workshop, sponsored by the National Kidney Foundation, gathered experts to address critical questions regarding patient outcomes, social determinants of health, individualised care, and the collection of patient-reported outcomes. The findings underscore significant gaps in the existing system and advocate for a flexible, adaptive quality programme that prioritises patient goals and social risk factors. This report is essential reading for professionals dedicated to enhancing the quality and patient-centredness of dialysis care.

2) Exploring systemic inflammation in children with chronic kidney disease: correlates of interleukin 6. Pediatr Nephrol 2024; 39:1567-1576. Karava V, Kondou A, Dotis J et al. Link to full article

The authors present a critical examination of biomarkers linked to systemic inflammation in paediatric patients with chronic kidney disease (CKD). This case-control and cross-sectional study rigorously investigates the relationship between interleukin-6 (IL-6) and various haematological and biochemical markers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC), and serum albumin. The findings highlight significant correlations, emphasising the relevance of these biomarkers in elucidating the inflammatory mechanisms in paediatric CKD. This article provides experts a better understanding of inflammatory markers and improve the clinical management of paediatric CKD.

3) γ-Gammaglutamyl transferase predicts all-cause mortality within three-year intervals in patients undergoing peritoneal dialysis. Ren Fail 2024; 46:2353339. Chen YB, Zhan XJ, Xiao J, Zhu HM. Link to full article

γ-Gammaglutamyl transferase is presented as a potential predictive biomarker, able to forecast all-cause mortality within three-year intervals in patients undergoing peritoneal dialysis. The authors present pivotal insights into the prognostic significance of γ-GGT in peritoneal dialysis patients. Conducted as a comprehensive retrospective study, it evaluates the correlation between γ-GGT levels and both cardiovascular and all-cause mortality over one, three, and five-year periods. The findings demonstrate significant differences in mortality rates based on γ-GGT levels, underscoring its potential as a predictive biomarker. This study offers crucial implications for improving patient outcomes in dialysis care, a “must read” for internists, nephrologists, and researchers in the field of renal medicine.

4) APOL1 Nephropathy Risk Variants Through the Life Course: A Review. Itoku A, Isaac J, Wilson S, Reidy K, Kaskel F. Am J Kidney Dis. 2024 Feb 9:S0272-6386(24)00597-3. doi: 10.1053/j.ajkd.2023.12.014. Online ahead of print. PMID: 38341125. Link to full article

This review provides an in-depth examination of the impact of APOL1 risk variants on kidney disease, particularly in individuals of African descent. By exploring the genetic, environmental, and systemic factors influencing disease progression from in utero stages to adulthood, this article offers a comprehensive understanding of how these risk variants contribute to kidney disease disparities. It discusses the interplay between genetic predispositions and environmental exposures, emphasising the need for early intervention and personalised treatment strategies. This review is of great value for nephrologists aiming to enhance their knowledge and improve clinical outcomes for nephropathy patients.

5) Leukocyturia and hematuria enable non-invasive differentiation of Bowman's capsule rupture severity in PR3-ANCA glomerulonephritis. J Nephrol 2023; 36:799-808. Baier E, Kluge IA, Hakroush S et al. Link to full article

Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody-(ANCA)-associated vasculitis, with a risk of rapid deterioration of kidney function and progression to end stage kidney disease due to pauci-immune necrotising and crescentic ANCA glomerulonephritis (GN). Routine urinary sediment analysis supports clinical management of ANCA GN but the histopathological implications of aberrations in the sediment are mostly unclear. In this study, 42 kidney biopsies with ANCA GN were retrospectively analysed in a single-centre observational study. Leukocyturia and haematuria were found to be associated with each other and with markers for non-selective glomerular damage. Non-invasive measurement of leukocyturia indicated focal (but not extensive) Bowman’s capsule rupture (BCR) specifically in proteinase-3 (PR3)-ANCA GN, whereas haematuria correlated with extensive (but not focal) BCR. Leukocyturia was also associated with tubulointerstitial plasma cell infiltration in PR3-ANCA GN. None of these associations were detectable in myeloperoxidase-ANCA GN, implying the existence of different modes of kidney damage.

6) Beyond conventional microscopy: Observing kidney tissues by means of fourier ptychography. Valentino M, Bianco V, Miccio L, et al. Front Physiol. 2023 Feb 13:14:1120099. doi: 10.3389/fphys.2023.1120099. eCollection 2023. PMID: 36860516. Link to full article

Observing kidney tissues by Fourier ptychography microscopy (FP) instead of conventional microscopy introduces an innovative approach to renal tissue analysis. This technique combines high resolution and wide field of view, providing unparalleled insights into kidney morphology without the need for staining. By comparing FP images with conventional light microscopy, the study demonstrates the significant advantages of FP in visualising unstained tissue structures, enhancing diagnostic accuracy, and potentially revolutionising clinical histopathology practices. This study is a crucial resource for researchers and clinicians, showing innovative imaging techniques, advancing renal pathology diagnostics, and improving patient care.