Kidney function assessment in the geriatric population.

PURPOSE OF REVIEW: Kidney function declines with normal aging. But it also declines with the progression of some diseases. This review calls for a more nuanced interpretation of kidney function in the geriatric population, who may have frailty and comorbidities. RECENT FINDINGS: GFR declines with healthy aging kidneys. Aging kidney changes include decreased cortical volume, senescent global glomerulosclerosis, and reduced nephron numbers. Yet normal aging is not associated with increased glomerular volume or single-nephron GFR. The prevalence of GFR less than 60 ml/min/1.73 m 2 in the geriatric population is high. However, the decline in GFR with normal aging may not reflect true CKD without albuminuria. Although the risk of ESKD and mortality increases in all age groups when eGFR less than 45 ml/min/m 2 , there is no significant increased relative risk of ESKD and mortality in the geriatric population when eGFR 45-59 ml/min/m 2 in the absence of albuminuria. Innovative approaches are needed to better estimate GFR and define CKD in the geriatric population. SUMMARY: The expected GFR decline in the geriatric population is consistent with normal aging kidney changes. To avoid CKD overdiagnosis and unnecessary referrals to nephrology for possible CKD, age-adapted definitions of CKD in the absence of albuminuria are needed.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Risk-based versus GFR threshold criteria for nephrology referral in chronic kidney disease.

Chronic kidney disease (CKD) and kidney failure are global health problems associated with morbidity, mortality and healthcare costs, with unequal access to kidney replacement therapy between countries. The diversity of guidelines concerning referral from primary care to a specialist nephrologist determines different outcomes around the world among patients with CKD where several guidelines recommend referral when the glomerular filtration rate (GFR) is <30 mL/min/1.73 m2 regardless of age. Additionally, fixed non-age-adapted diagnostic criteria for CKD that do not distinguish correctly between normal kidney senescence and true kidney disease can lead to overdiagnosis of CKD in the elderly and underdiagnosis of CKD in young patients and contributes to the unfair referral of CKD patients to a kidney specialist. Non-age-adapted recommendations contribute to unnecessary referral in the very elderly with a mild disease where the risk of death consistently exceeds the risk of progression to kidney failure and ignore the possibility of effective interventions of a young patient with long life expectancy. The opportunity of mitigating CKD progression and cardiovascular complications in young patients with early stages of CKD is a task entrusted to primary care providers who are possibly unable to optimally accomplish guideline-directed medical therapy for this purpose. The shortage in the nephrology workforce has classically led to focused referral on advanced CKD stages preparing for kidney replacement, but the need for hasty referral to a nephrologist because of the urgent requirement for kidney replacement therapy in advanced CKD is still observed and changes are required to move toward reducing the kidney failure burden. The Kidney Failure Risk Equation (KFRE) is a novel tool that can guide wiser nephrology referrals and impact patients.

Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies.

BACKGROUND: Semiquantitative visual inspection for glomerulosclerosis, interstitial fibrosis, and arteriosclerosis is often used to assess chronic changes in native kidney biopsies. Morphometric evaluation of these and other chronic changes may improve the prognostic assessment. METHODS: We studied a historical cohort of patients who underwent a native kidney biopsy between 1993 and 2015 and were followed through 2021 for ESKD and for progressive CKD (defined as experiencing 50% eGFR decline, temporary dialysis, or ESKD). Pathologist scores for the percentages of globally sclerosed glomeruli (GSG), interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis (luminal stenosis) were available. We scanned biopsy sections into high-resolution images to trace microstructures. Morphometry measures were percentage of GSG; percentage of glomerulosclerosis (percentage of GSG, ischemic-appearing glomeruli, or segmentally sclerosed glomeruli); percentage of IFTA; IFTA foci density; percentage of artery luminal stenosis; arteriolar hyalinosis counts; and measures of nephron size. Models assessed risk of ESKD or progressive CKD with biopsy measures adjusted for age, hypertension, diabetes, body mass index, eGFR, and proteinuria. RESULTS: Of 353 patients (followed for a median 7.5 years), 75 developed ESKD and 139 experienced progressive CKD events. Visually estimated scores by pathologists versus morphometry measures for percentages of GSG, IFTA, and luminal stenosis did not substantively differ in predicting outcomes. However, adding percentage of glomerulosclerosis, IFTA foci density, and arteriolar hyalinosis improved outcome prediction. A 10-point score using percentage of glomerulosclerosis, percentage of IFTA, IFTA foci density, and any arteriolar hyalinosis outperformed a 10-point score based on percentages of GSG, IFTA, and luminal stenosis >50% in discriminating risk of ESKD or progressive CKD. CONCLUSION: Morphometric characterization of glomerulosclerosis, IFTA, and arteriolar hyalinosis on kidney biopsy improves prediction of long-term kidney outcomes.

Precision medicine for the treatment of glomerulonephritis: a bold goal but not yet a transformative achievement.

The revolution in our ability to recognize the alterations in fundamental biology brought about by disease has fostered a renewed interest in precision or personalized medicine ('the right treatment, or diagnostic test, for the right patient at the right time'). This nascent field has been led by oncology, immunohematology and infectious disease, but nephrology is catching up and quickly. Specific forms of glomerulonephritis (GN) thought to represent specific 'diseases' have been 'downgraded' to 'patterns of injury'. New entities have emerged through the application of sophisticated molecular technologies, often embraced by the term 'multi-omics'. Kidney biopsies are now interpreted by next-generation imaging and machine learning. Many opportunities are manifest that will translate these remarkable developments into novel safe and effective treatment regimens for specific pathogenic pathways evoking GN and its progression to kidney failure. A few successes embolden a positive look to the future. A sustained and highly collaborative engagement with this new paradigm will be required for this field, full of hope and high expectations, to realize its goal of transforming glomerular therapeutics from one size fits all (or many) to a true individualized management principle.

Healthy and unhealthy aging on kidney structure and function: human studies.

PURPOSE OF REVIEW: This review is intended to provide an up-to-date analysis of the structural and functional alterations of the kidneys that accompany healthy and unhealthy aging in humans. Macro- and micro- structural changes and glomerular filtration rate (whole kidney and single nephron) accompanying aging will be stressed. RECENT FINDINGS: Comparative findings concerning distribution of anatomic changes of the kidney healthy and unhealthy aging are reviewed. Challenges concerning definition of chronic kidney disease (CKD) in otherwise healthy aging patients are discussed. The complex interactions of CKD and aging are discussed. The role of podocyte dysbiosis in kidney aging is reviewed. SUMMARY: Kidney aging is a complex phenomenon often difficult to distinguish from CKD. Nonetheless, phenotypes of healthy and unhealthy aging are evident. Much more information concerning the molecular characteristics of normal kidney aging and its relevance to chronic kidney disease is needed.