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Kidney biopsy is an established standard approach for the histopathological diagnosis of kidney diseases, with additional information also available for determining a therapeutic intervention strategy and predicting kidney disease outcomes. [...]far, biopsy specimens have been used for various morphometric analyses of the kidneys, mainly for research purposes [1-4]. [...]glomerular enlargement in diagnostic kidney biopsy has been consistently identified as a hallmark of worse kidney outcomes in a series of etiologically different kidney diseases in previous studies [1-3]. [...]studies on autopsy series without apparent kidney diseases have disclosed that the human nephron number varies significantly between individuals and is inversely correlated with glomerular size [10]. Consistent with the hypothesis of glomerular adaptation failure raised by experimental animal studies using a kidney ablation model [7], the innate or acquired reduction of the nephron number has been linked to enlarged glomerular size in many studies [10].

Chronic kidney disease (CKD) is one of the strongest risk factors for hypertension, and hypertension can exacerbate the progression of CKD. Thus, the management of CKD and antihypertensive therapy are inextricably linked. Research over the past decades has shown that the human kidney is more diverse than initially thought. Subjects with low nephron endowment are at increased risk of developing CKD and hypertension, which is consistent with the theory of the developmental origins of health and disease. Combined with other lifetime risks of CKD, hypertension may lead to a vicious cycle consisting of podocyte injury, glomerulosclerosis and further loss of nephrons. Of note, recent studies have shown that the number of nephrons correlates well with the number of podocytes, suggesting that these two components are intrinsically linked and may influence each other. Both nephrons and podocytes have no or very limited regenerative capacity and are destined to decrease throughout life. Therefore, one of the best strategies to slow the progression of CKD is to maintain the “numbers” of these essential components necessary to preserve renal function. To this end, both the achievement of an optimal blood pressure and a maximum reduction in urinary protein excretion are essential. Lifestyle modifications and antihypertensive drug therapy must be carefully individualized to address the potential diversity of the kidneys.

Total nephron counts vary widely between individuals and may affect susceptibility to certain diseases, including hypertension and chronic kidney disease. Detailed analyses of whole kidneys collected from autopsy patients remain the only method for accurately counting nephrons in humans, with no equivalent option in living subjects. Current technological advances have enabled estimations of nephron numbers in vivo, particularly the use of total nephron number and whole-kidney glomerular filtration rate to estimate the mean single-nephron glomerular filtration rate. The use of this method would allow physicians to detect dynamic changes in filtration function at the single-nephron level rather than to simply count the number of nephrons that appear to be functioning. Currently available methods for estimating total nephron number in clinical practice have the potential to overcome limitations associated with autopsy analyses and may therefore pave the way for new therapeutic interventions and improved clinical outcomes.

[This corrects the article DOI: 10.1371/journal.pone.0250581.].[This corrects the article DOI: 10.1371/journal.pone.0250581.].

Data on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce. This study retrospectively analyzed clinical variables in patients with stage G1-G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June-July 2020) were compared to those one year before the pandemic (term 0, June-July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure. This study included 325 patients with stage G1-G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92-624) and 203 (84-508) mg/day [median (25th-75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p<0.001), with no marked difference in body weight, blood pressure, protein intake or urinary salt excretion. In multivariable analyses, incomplete remission of proteinuria in term 0 (odds ratio [OR] = 2.70, p = <0.001), RAASi use (OR = 2.09, p = 0.02) and decreased urinary salt excretion in term 1 vs. term 0 (OR = 1.94, p = 0.002) were identified as independent variables associated with reduced UPE in term 1 vs. term 0. No significant interactions between the variables were observed. In kidney disease patients receiving standard medical care from nephrologists, the UPE after the emergency declaration in relation to the COVID-19 pandemic was lower than before the declaration. The UPE reduction may be associated with reduced dietary salt intake during the pandemic in patients treated with RAASi for insufficient control of proteinuria. Our results support the current proposal to continue therapeutic approaches to these patients, which involve RAASi therapy along with optimizing dietary habits, even while dealing with the COVID-19 pandemic.

Gross hematuria (GH) following COVID-19 mRNA vaccination has been increasingly reported in patients with IgA nephropathy (IgAN). This study assessed the effect of post-vaccination GH on kidney function. A total of 441 Japanese outpatients with biopsy-confirmed IgAN (median age: 51 years; 56% female; baseline eGFR: 57 mL/min/1.73 m²) were classified into three groups: unvaccinated ( n  = 25), vaccinated without GH ( n  = 391), and vaccinated with GH ( n  = 25). Kidney function was evaluated at approximately 1 year (midpoint) and 2 years (endpoint) after baseline. The annual eGFR change (ΔeGFR: mL/min/1.73 m²/year) at midpoint was − 1.16, − 1.03, and − 2.50, respectively. The GH group showed a significantly greater decline compared to the non-GH group ( p  = 0.015), and GH was significantly associated with greater eGFR decline at midpoint (odds ratio: 2.97, p  = 0.038). At the endpoint, the ΔeGFR was − 0.45, − 1.93, and − 1.72, with no significant differences among the groups ( p  = 0.773). In this cohort, GH after vaccination was observed to be associated with a greater short-term decline in kidney function, although the retrospective design precludes establishing causality.

Ammonium excretion is often estimated using urinary anion gap (UAG) and osmolality gap (UOG) when direct measurement is unavailable, particularly in patients with impaired kidney function. We aimed to examine how UAG and UOG vary across different levels of kidney function and their relationships with acid–base parameters. This retrospective cohort study included 531 outpatients categorized by estimated glomerular filtration rate (eGFR: ≥ 90, 60–89, 45–59, 30–44, and < 30 mL/min/1.73 m 2 ). UAG values increased significantly with declining eGFR (p = 0.002), whereas UOG showed no clear trend (p = 0.303). UAG correlated positively with serum pH (ρ = 0.135, p = 0.002) and urinary pH (ρ = 0.333, p < 0.001). UOG was strongly inversely correlated with urinary pH (ρ = -0.512, p < 0.001). Sensitivity analyses stratified by serum anion gap and bicarbonate substantiated UAG’s relationship with eGFR. Multivariate analyses confirmed UAG’s association with eGFR, serum pH, and urinary pH, whereas UOG was predominantly influenced by urinary pH and minimally by eGFR. Although UOG has traditionally been considered superior, our findings suggest that UAG demonstrated more consistent associations with kidney function parameters. However, direct NH₄⁺ measurements remain necessary for definitive clinical assessment.

Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN. The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated. In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis. The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.