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A two-and-a-half-month-old female infant presented with generalized edema for 10 days. At presentation, she had periorbital puffiness, moderate ascites, and pedal edema. Laboratory investigations revealed serum albumin 1.3 g/dL, spot urine protein to creatinine ratio (Up:Uc) 20.87 mg/mg, total cholesterol 380 mg/dL, and serum creatinine 0.31 mg/dL. Exome sequencing revealed compound heterozygous variants in LAMA5 gene (NM_005560.6). There was a heterozygous likely pathogenic missense variant in exon 2: LAMA5: c.385C > A (depth 195 ×) and another heterozygous pathogenic variant in exon 31: LAMA5: c.3932_3936dup; parental segregation by Sanger sequencing proved that the variants were in trans. Kidney biopsy showed diffuse mesangial sclerosis (DMS). Our case adds LAMA5 gene to the constellation of genes causing DMS, in addition to the classically described WT1, LAMB2, and PLCE1 genes and to the list of genes causing congenital nephrotic syndrome (CNS). [ABSTRACT FROM AUTHOR]

Introduction: The non-neoplastic kidney parenchyma from nephrectomies is often overlooked in routine examinations. We aimed to evaluate the associations between global glomerulosclerosis (GS), interstitial fibrosis (IF), or arteriosclerosis (AS) and estimated glomerular filtration rate (eGFR), dipstick proteinuria, and other clinical factors. Methods: We performed a cross-sectional analysis of 781 patients with nephrectomy. We used regression models with and without interaction factors. The tested exposures were GS, IF, or AS, and the outcome measures were GFR and dipstick proteinuria. Results: In multivariable analyses, increasing degrees of GS, IF, or AS were significantly associated with lower eGFR and proteinuria (p < 0.05 for each). Obesity and hypertension (HTN) modified the association between eGFR and degrees of GS, whereas proteinuria and cardiovascular disease (CVD) modified the association between eGFR and degrees of AS (p for interaction 50% was associated with lower eGFR in patients with (−45 mL/min/1.73 m2) than without (−19 mL/min/1.73 m2) obesity, and GS >50% was associated with lower eGFR in patients with (−31 mL/min/1.73 m2) than without (−16 mL/min/1.73 m2) HTN. Compared with AS 50% was associated with lower eGFR in patients with (−11 mL/min/1.73 m2) than without (−6 mL/min/1.73 m2) proteinuria, and AS >50% was associated with lower eGFR in patients with (−23 mL/min/1.73 m2) than without (−7 mL/min/1.73 m2) CVD. Conclusion: Greater degrees of each GS, IF, and AS are independently associated with proteinuria and lower eGFR. Obesity, HTN, proteinuria, and CVD modify the relationship between eGFR and specific histopathological features of nephrosclerosis.

Background Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood. Methods To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985–2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy. Results A total of 114 patients were included, 77 (67%) of whom were men, average age 34 years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34–1.96], P  < .001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53–112.03), P  = .03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02–0.60), P  = .01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity. Conclusions This suggests that kidney biopsy might be beneficial in young patients with MH. [ABSTRACT FROM AUTHOR]

Background:The diagnosis of kidney diseases still highly depends on kidney biopsies, despite advancements in non-invasive chemical and imaging diagnostics. This research aims to study the frequency of different types of kidney diseases through histopathological findings of kidney biopsies and to evaluate the outcomes of different pathological patterns. Methods:This prospective observational cohort study involved 56 patients who indicated renal biopsy from January 2022 to June 2022. Percutaneous, ultrasound-guided percutaneous core needle biopsies were performed in the prone position. Two kidney biopsy core specimens were obtained. The biopsy tissues were prepared on routine standard protocols for histopathology using light microscopy and immunohistochemistry. Follow up of patients was done for 6 months regarding response to treatment and disease outcome. Results:56 patients were included, their mean age was 36.6±14.1 years. 12.5% of patients presented with sub-nephrotic proteinuria, 23% of patients presented with sub-nephrotic proteinuria with renal impairment, 23% presented with nephrotic syndrome, 30% of patients presented with nephrotic proteinuria with renal impairment. The most common pathological findings were focal segmental glomerulosclerosis (FSGS) (25%) followed by lupus nephritis (LN) (19.6%). The most prevalent pathological lesions in the young age group were LN and MCD while in the older age group were hypertensive nephrosclerosis and diabetic nephropathy (DN). Conclusions:FSGS and LN were the most prevalent patterns. The most common pathological patterns at a young age were MCD followed by LN and FSGS. While the most common pattern in the older age group was DN and hypertensive nephrosclerosis. Partial and complete remission had been seen in 38.3% of all pathological lesions. [ABSTRACT FROM AUTHOR]

Aim: Age‐standardized incidence of end stage kidney disease requiring renal replacement therapy (RRT) has stabilized in men and declined in women in Japan since 1996. However, recent trends by primary kidney disease are unknown. The present study aimed to examine recent trends in incidence rates of RRT by primary kidney disease in Japan. Methods: Numbers of incident RRT patients aged ≥20 years by sex and primary kidney disease from 2006 to 2020 were extracted from the Japanese Society of Dialysis Therapy registry. Using the census population as the denominator, annual incidence rates of RRT were calculated and standardized to the WHO World Standard Population (2000–2025). Average annual percentage change (AAPC) and corresponding 95% confidence intervals (CIs) were calculated for trends using Joinpoint regression analysis. Results: From 2006 to 2020, the crude number of incident RRT patients due to nephrosclerosis increased by 132% for men and 62% for women. Age‐standardized incidence rates of RRT due to nephrosclerosis increased significantly, by 3.3% (95% CI: 2.9–3.7) and 1.4% (95% CI: 0.8–1.9) per year for men and women, respectively. The AAPC of chronic glomerulonephritis (−4.4% [95% CI: −5.3 to −3.8] for men and −5.1% [95% CI: −5.5 to −4.6] for women) and diabetic nephropathy (−0.6% [95% CI: −0.9 to −0.3] for men and −2.8% [95% CI: −3.1 to −2.6] for women) significantly decreased from 2006 to 2020. Conclusion: Incident RRT due to chronic glomerulonephritis and diabetic nephropathy decreased, while the number and incident rates of RRT due to nephrosclerosis increased, from 2006 to 2020 in Japan. Summary at a Glance: Using data from the Japanese Society of Dialysis Therapy registry between 2006 and 2020, this study demonstrated that age‐standardized incidence rates of end stage kidney disease requiring renal replacement therapy (RRT) due to chronic glomerulonephritis and diabetic nephropathy decreased, while rates due to nephrosclerosis increased, considerably in Japan. Age‐specific incidence rates of RRT attributed to nephrosclerosis also increased in many age groups, suggesting that the increased number of patients with nephrosclerosis as the primary kidney disease is not only due to the increasing number of older people but also increasing age‐specific incidence rates. [ABSTRACT FROM AUTHOR]

The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible to the aging process. Unfavorable conditions may lead to a significant disturbance of the body's homeostasis. Apart from physiological changes, there are some conditions such as hypertension, diabetes or obesity which contribute to the acceleration of the aging process. A determination of macroscopic and microscopic changes is essential for assessing the progression of aging. With age, we observe a decrease in the volume of renal parenchyma and an increase in adipose tissue in the renal sinuses. Senescence may also be manifested by the roughness of the kidney surface or simple renal cysts. The main microscopic changes are a thickening of the glomerular basement membrane, nephrosclerosis, an accumulation of extracellular matrix, and mesangial widening. The principal aspect of stopping unfavorable changes is to maintain health. Studies have shown many useful ways to mitigate renal aging. This review is focused especially on medications such as renin-angiotensin-aldosterone system blockers or resveratrol, but even eating habits and lifestyle. [ABSTRACT FROM AUTHOR]

Hypertension, aging, and other factors are associated with arteriosclerosis and arteriolosclerosis, primary morphological features of nephrosclerosis. Although such pathological changes are not invariably linked with renal decline but are prevalent across chronic kidney disease (CKD), understanding kidney damage progression is more pragmatic than precisely diagnosing nephrosclerosis itself. Hyalinosis and medial thickening of the afferent arteriole, along with intimal thickening of small arteries, can disrupt the autoregulatory system, jeopardizing glomerular perfusion pressure given systemic blood pressure (BP) fluctuations. Consequently, such vascular lesions cause glomerular damage by inducing glomerular hypertension and ischemia at the single nephron level. Thus, the interaction between systemic BP and afferent arteriolopathy markedly influences BP-dependent renal damage progression in nephrosclerosis. Both dilated and narrowed types of afferent arteriolopathy coexist throughout the kidney, with varying proportions among patients. Therefore, optimizing antihypertensive therapy to target either glomerular hypertension or ischemia is imperative. In recent years, clinical trials have indicated that combining renin-angiotensin system inhibitors (RASis) and sodium-glucose transporter 2 inhibitors (SGLT2is) is superior to using RASis alone in slowing renal function decline, despite comparable reductions in albuminuria. The superior efficacy of SGLT2is may arise from their beneficial effects on both glomerular hypertension and renal ischemia. A comprehensive understanding of the interaction between systemic BP and heterogeneous afferent arteriolopathy is pivotal for optimizing therapy and mitigating renal decline in patients with CKD of any etiology. Therefore, in this comprehensive review, we explore the role of afferent arteriolopathy in BP-dependent renal damage., (© 2024. The Author(s).)

A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses (diabetic kidney disease, glomerulonephritis, and nephrosclerosis) as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: The aim of this autopsy study was to clarify the differences of renal histopathology between non-chronic kidney disease (CKD) and CKD caused by hypertensive-nephrosclerosis in the elderly and during the aging process. Methods: We examined autopsy specimens from 105 elderly patients (53 male subjects; mean age, 86.2 years) including 44 patients with CKD as a result of nephrosclerosis. The analysis was divided into two groups depending on whether they had CKD. Results: The incidences of arterial intimal thickening (AIT), obsolescent-type global glomerulosclerosis (OB), and interstitial fibrosis and tubular atrophy (IF/TA) were higher in the CKD group than in the non-CKD group (all p < 0.01). These factors were all correlated with each other (AIT vs. OB, r = 0.43; AIT vs. IF/TA, r = 0.25; OB vs. IF/TA, r = 0.53). IF/TA had the strongest association with hypertension and decreased eGFR. In the non-CKD group, the frequency of OB was more than 20% in subjects aged 90 years or older. However, the individuals in the non-CKD group tended to have compensatory glomerular hypertrophy with increasing age and a retained eGFR, while the CKD group was unable to obtain compensatory hypertrophy and had a lower eGFR. We also found that AIT, OB and IF/TA occurred independently of systemic atherosclerosis. Conclusions: Non-CKD in the elderly refers to the so-called aging kidney. The progression from aging kidney to CKD caused by nephrosclerosis was influenced by increases in AIT, OB and IF/TA. IF/TA was thought to be the most important downstream factor in the progression of aging kidney to CKD. [ABSTRACT FROM AUTHOR]

[Display omitted] • GFR slope in DKD group was steeper than in non-DKD with diabetes (NDKD + DM) group. • GFR slope in DKD group was steeper than in nephrosclerosis (NS) group. • GFR slope was equivalent between NDKD + DM and NS groups. • Risk of rapid GFR decline in NS group was high even with low proteinuria (UPCR). • Upon UPCR matching, UPCR's impact on rapid GFR decline was similar in DKD and NS. It is unclear whether the effect of proteinuria on rapid kidney function decline is equivalent among diabetic kidney disease (DKD), non-DKD with diabetes (NDKD+DM), and nephrosclerosis without diabetes (NS-DM), particularly in advanced chronic kidney disease patients. In total, 1038 chronic kidney disease patients who participated in the BRIGHTEN study were included in the present study. A linear mixed effect model was applied to estimate the annual estimated glomerular filtration rate decline in each disease group. The prevalence of rapid decliners (rapid kidney function decline, defined as an eGFR loss of > 5 mL/min/1.73 m2/year) in the DKD group (44.6 %) was significantly higher compared with the NDKD+DM (27.9 %) and NS-DM (27.0 %) groups. By contrast, the prevalence of rapid decliners in different urine total protein to creatinine ratio (UPCR) categories (<0.5, 0.5 to < 1.0, 1.0 to < 3.5, and ≥ 3.5 g/g) were equivalent between the DKD and NS-DM groups. Moreover, the prevalence of a UPCR < 1.0 g/g in rapid decliners of the NS-DM group was more than double than in those of the DKD and NDKD+DM groups. The risk of rapid kidney function decline in NS-DM patients with low levels of proteinuria may be greater than initially predicted. [ABSTRACT FROM AUTHOR]

Nephrosclerosis patients have a high cardiovascular (CV) risk that is very often of more concern than the renal disease itself. We aimed to determine whether variants in phospholipase-related genes, associated with atherosclerosis and CV outcomes in the general population, could constitute biomarkers of nephrosclerosis and/or its associated CV risk. We screened 1,209 nephrosclerosis patients and controls for 86 tag-SNPs that were identified in the SCARB1 , PLA2G4A, and PLA2G7 gene loci. Regression models were utilized to evaluate their effect on several clinical parameters. Most notably, rs10846744 and rs838880 in SCARB1 showed significant odds ratios (OR) of 0.66 (0.51–0.87), p = 0.003 and 1.48 (1.11–1.96), p = 0.007 for nephrosclerosis risk. PLA2G4A and PLA2G7 harboured several SNPs associated with atherosclerosis measurements in the patients, namely common carotid intima media thickness (ccIMT), presence of plaques, number of plaques detected and 2-years ccIMT progression (significant p -values ranging from 0.0004 to 0.047). Eight SNPs in PLA2G4A were independent risk factors for CV events in nephrosclerosis patients. Their addition to a ROC model containing classic risk factors significantly improved its predictive power from AUC = 69.1% (61.4–76.9) to AUC = 79.1% (73.1–85.1%), p = 0.047. Finally, PLA2G4A rs932476AA and rs6683619AA genotypes were associated with lower CV event-free survival after controlling for confounding variables [49.59 (47.97–51.21) vs. 51.81 (49.93–51.78) months, p = 0.041 and 46.46 (41.00–51.92) vs. 51.17 (50.25–52.08) months, p = 0.022, respectively]. Variability in phospholipase-related genes play a relevant role in nephrosclerosis and associated atherosclerosis measurements and CV events. [ABSTRACT FROM AUTHOR]

Background: Patients with nephrosclerosis display heterogenous clinical phenotypes, often leading to a clinical diagnosis discordant with pathological nephrosclerosis diagnosis. However, little is known about clinical factors associated with clinicopathological discordance of biopsy-proven nephrosclerosis. Methods: In a cross-sectional study of 891 patients with biopsy-proven nephrosclerosis registered in the Japan Renal Biopsy Registry (J-RBR) between July 2007 and June 2016, we examined clinical characteristics associated with a pre-biopsy clinical diagnosis discordant with pathological nephrosclerosis diagnosis using multivariable logistic regression with adjustment for relevant clinical characteristics. Results: Overall, the mean (SD) age was 58.6 (13.7) years; 67.6% of patients were male; and 63.2% were on antihypertensive drugs. The median estimated glomerular filtration rate (eGFR) was 43.8 mL/min/1.73 m2 and the median proteinuria was 0.5 g/day. Of the 891 patients, 497 (55.8%) had a clinical diagnosis discordant with pathological nephrosclerosis diagnosis, with chronic nephritic syndrome being the most common (> 75%) discordant clinical diagnosis. After multivariable adjustment, age (odds ratio 1.34, [95% confidence interval, 1.16–1.55], per 10 years increase), eGFR (1.10 [1.00–1.21], per 10 mL/min/1.73 m2 increase), and proteinuria (1.20 [1.03–2.16], per 1 g/day decrease) were found to be significantly associated with the clinicopathological discordance. Conclusions: Patients with older age, higher eGFR, and lower proteinuria had significantly higher likelihood of being clinically diagnosed with other glomerular disease in patients with biopsy-proven nephrosclerosis. Our findings highlight the heterogeneous clinical phenotypes of nephrosclerosis and suggest the need for continuous improvement of clinical diagnostic accuracy as well as for wider kidney biopsy indications for nephrosclerosis. [ABSTRACT FROM AUTHOR]

Background and purpose: We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA). Methods: We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990–1999 (n = 48); period 2, 2000–2009(n = 57); period 3, 2010–2019 (n = 51). Results: Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010–2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1–3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time. Conclusion: Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA. [ABSTRACT FROM AUTHOR]

This longitudinal study with a randomized controlled trial evaluated the long-term effectiveness of the patient-centered self-management intervention program on the control of blood pressure and renal function, as well as the quality of life of patients with hypertensive nephropathy. The control group (n = 38) received usual care while the experimental group (n = 38) participated in a patient-centered self-management program. After the pre-test, the intervention was performed with the experimental group once a week for a total of 4 weeks. Then, the post-test was performed 1, 3, and 6 months later. A questionnaire was used to collect the demographic data and disease characteristics, laboratory data, and quality of life scale. This study tracked three time points (i.e., 1, 3, and 6 months) after the intervention and found that the experimental group achieved significant results in controlling systolic blood pressure (p < 0.001), diastolic blood pressure (p = 0.007), and eGFR (p = 0.013). Significant results were achieved in the overall quality of life (p < 0.001) and the quality of life in the physical (PHC; p < 0.001) and mental health components (MHC; p < 0.001). Furthermore, the effects in the experimental group lasted for as long as 6 months and were better than those in the control group. Moreover, this program can provide nursing staff with a reference different from traditional health education methods. [ABSTRACT FROM AUTHOR]

In a retrospective study of a western pygmy marmoset (Cebuella pygmaea) colony, postmortem examination of 1/8 juvenile and 29/47 adult animals identified vascular, cardiac, and renal lesions consistent with systemic hypertension. This included frequent renal arteriolar hypertrophy, hyaline and proliferative arteriolosclerosis, fibrinoid necrosis of arterioles, glomerulosclerosis, and nephrosclerosis. Affected animals ranged from 0.6 to 12 years of age (mean 6 years) and had an observed male predominance. Genealogical relatedness was evident in several breeding pairs and spanned multiple generations. Concurrent cardiac and renal disease was commonly identified, although frequently subclinical, and both were important causes of morbidity and mortality in affected animals. Cardiomegaly and hypertrophy were typical features and were accompanied by left atrial thrombosis in 10 animals. Signs of heart failure included chronic pulmonary edema in 20 cases and body cavity effusions in 17. In the kidneys, 19 cases had glomerular disease and hypertensive vasculopathy, and 26 cases had nephrosclerosis or glomerulosclerosis. Common extrarenal secondary causes of hypertension were excluded by necropsy examination. The pathogenesis is suggested to involve primary hypertension leading to renal and cardiac disease. Elevated sympathetic activity might be an underlying factor in the frequent development of primary systemic hypertension in the pygmy marmoset, as for the owl monkey. [ABSTRACT FROM AUTHOR]

Nephrosclerosis patients have a high cardiovascular (CV) risk that is very often of more concern than the renal disease itself. We aimed to determine whether variants in phospholipase-related genes, associated with atherosclerosis and CV outcomes in the general population, could constitute biomarkers of nephrosclerosis and/or its associated CV risk. We screened 1,209 nephrosclerosis patients and controls for 86 tag-SNPs that were identified in the SCARB1, PLA2G4A, and PLA2G7 gene loci. Regression models were utilized to evaluate their effect on several clinical parameters. Most notably, rs10846744 and rs838880 in SCARB1 showed significant odds ratios (OR) of 0.66 (0.51–0.87), p = 0.003 and 1.48 (1.11–1.96), p = 0.007 for nephrosclerosis risk. PLA2G4A and PLA2G7 harboured several SNPs associated with atherosclerosis measurements in the patients, namely common carotid intima media thickness (ccIMT), presence of plaques, number of plaques detected and 2-years ccIMT progression (significant p-values ranging from 0.0004 to 0.047). Eight SNPs in PLA2G4A were independent risk factors for CV events in nephrosclerosis patients. Their addition to a ROC model containing classic risk factors significantly improved its predictive power from AUC = 69.1% (61.4–76.9) to AUC = 79.1% (73.1–85.1%), p = 0.047. Finally, PLA2G4A rs932476AA and rs6683619AA genotypes were associated with lower CV event-free survival after controlling for confounding variables [49.59 (47.97–51.21) vs. 51.81 (49.93–51.78) months, p = 0.041 and 46.46 (41.00–51.92) vs. 51.17 (50.25–52.08) months, p = 0.022, respectively]. Variability in phospholipase-related genes play a relevant role in nephrosclerosis and associated atherosclerosis measurements and CV events.

All forms of progressive renal diseases develop a final pathway of tubulointerstitial fibrosis and glomerulosclerosis. Renal fibrosis is usually quantified using histological staining, a process that is time-consuming and pathologist dependent. Here we develop a fast and operator-independent method to measure fibrosis utilizing the murine unilateral ureteral obstruction model which manifests a time-dependent fibrotic increase in obstructed kidneys while the contralateral kidneys are used as controls. After ureteral obstruction, kidneys were analyzed at 7, 14, and 21 days. Fibrosis was quantified using fluorescence lifetime imaging (FLIM) and second harmonic generation (SHG) in a Deep Imaging via Enhanced photon Recovery deep tissue imaging microscope. This microscope was developed for deep tissue along with second and third harmonic generation imaging and has extraordinary sensitivity toward harmonic generation. SHG data suggest the presence of more fibrillar collagen in the obstructed kidneys. The combination of short-wavelength FLIM and SHG analysis results in a robust assessment procedure independent of observer interpretation and let us create criteria to quantify the extent of fibrosis directly from the image. Thus, the FLIM-SHG technique shows remarkable improvement in quantification of renal fibrosis compared to standard histological techniques.

Introduction: Information regarding the influence of serum uric acid (SUA) levels on pathological changes in the kidney is limited. In this study, we examined the association between SUA levels and pathological findings of nephrosclerosis in population-based autopsy samples.Methods: A total of 923 deceased individuals in a Japanese community underwent autopsy examinations between 1974 and 1994. Of these, 547 individuals with available kidney tissues and health examination data within a median of 3 years before death were eligible for the present study. SUA levels were categorized into quintiles (Q1, 107-237; Q2, 238-279; Q3, 280-326; Q4, 327-380; Q5, 381-755 μmol/L). Advanced degrees of glomerular sclerosis, kidney arteriolar hyalinosis, and kidney arteriosclerosis were defined as the 90th percentile or more of a glomerular sclerosis index and an arteriolar hyalinosis index, and the 10th percentile or less of a wall-lumen ratio, respectively. A logistic regression model was used to evaluate odds ratios (ORs) and their 95% confidence intervals (CIs) of SUA levels on each kidney lesion.Results: Higher SUA levels were significantly associated with higher values of the age- and sex-adjusted glomerular sclerosis index and lower values of the wall-lumen ratio (both p for trend <0.01). Individuals in the Q5 group had a significantly greater likelihood of advanced glomerular sclerosis (OR 7.19, 95% CI 2.42-21.38) and advanced kidney arteriosclerosis (OR 5.28, 95% CI 1.77-15.80) than individuals in the Q1 group after adjusting for potential covariates. There was no evidence of significant associations of SUA levels with either the arteriolar hyalinosis index or the presence of advanced arteriolar hyalinosis.Conclusions: Elevated SUA levels were significantly associated with advanced glomerular sclerosis and advanced kidney arteriosclerosis, but not with advanced arteriolar hyalinosis in community-based autopsy samples of Japanese. [ABSTRACT FROM AUTHOR]

Aim: To explore the possibility of using urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assess the presence of renal scars in children with Vesicoureteric Reflux (VUR). Materials and Methods: This cross-sectional study was conducted in 94 children aged 0–16 years diagnosed with VUR in the Department of Pediatric Surgery, JIPMER. Urinary biomarkers were measured using the enzyme-linked immunosorbent assay kits, normalized with urinary creatinine (Cr) and compared with severity of VUR (low grade [I and II] and high grade [III, IV, and V]), presence or absence of renal scar in VUR patients and severity of renal scar. Independent Student's t-test, Mann–Whitney U-test, and analysis of variance Kruskal–Wallis test were used for comparison, and receiver operating characteristic (ROC) curve analysis for predicting the accuracy of biomarkers in detecting the presence of renal scars. Results: The median urinary NGAL (uNGAL) value was higher in children with renal scar (1.49 ng/mL) than those without renal scar (0.58 ng/mL) and was statistically significant (<0.001). Whereas median uNGAL/Cr was higher in children with renal scar (0.07) than those without renal scar (0.03) but was not statistically significant (P = 0.06). Urinary KIM-1 and urinary KIM-1/urinary Cr (uKIM-1/Cr) was not found to be a significant predictor of renal scar. The difference of uNGAL/Cr was comparable between the grades of renal scar but was not statistically significant. On ROC curve analysis, uNGAL had area under the ROC curve (AUC) of 0.769 with 71% of both specificity and sensitivity, whereas uNGAL/Cr was found to be a poor predictor of renal scar with AUC of 0.611, 60% sensitivity, and 61.2% specificity. Conclusion: uNGAL can serve as a noninvasive marker for diagnosing the presence of renal scar in children with VUR and a multicentric more extensive cohort study may be needed to strengthen or negate its role. [ABSTRACT FROM AUTHOR]

The elderly population experiences a normal, age-related decline of physiological function in all major organ systems. The age-related changes in lung structure include decreases in chest wall compliance, respiratory muscle strength and elastic recoil, contributing to decreased lung function which increases susceptibility to infection. The age-related changes in cardiovascular structure and function increases the risk of cardiovascular disease. The aging process in the kidney leads to several clinical conditions in the elderly such as impaired drug metabolism and kinetics, loss of homeostasis, and electrolyte abnormalities. With aging, the decrease in gastrointestinal (GI) function in the mouth, esophagus, stomach, small and large intestine, and liver may affect appetite, motility, enzyme and hormone secretion, nutrient digestion and absorption, and gastrointestinal immunity. These changes in GI function may play a significant role in malnutrition and an increased risk of cachexia. Aging leads to inevitable deterioration in cellular and physiological function, which result in impaired homeostasis, decreased ability to adapt to stress, increased vulnerability to disease, and increased age-related mortality. Optimal health care management requires a deep understanding of the normal physiological changes associated with aging, and is necessary to provide insight into the mechanisms of multiple organ impairment and disease in the elderly.

Background/Aims This study aimed to investigate long-term temporal trends and outcomes of biopsy-proven kidney diseases in a multicenter kidney biopsy cohort, focusing on hypertension and diabetes, the leading causes of end-stage kidney disease (ESKD). Methods The study included a total of 21,426 patients who underwent kidney biopsy from 1979 to 2018 in 18 hospitals in Korea. We selected subgroups of adults with diabetes (n = 2,813) or clinically presumed hypertensive nephrosclerosis (HT-N, n = 2,917). Clinical, demographic, and laboratory data were collected in conjunction with pathologic findings. The prevalence of pathologically confirmed kidney diseases over time and their associations with clinical outcomes were evaluated. Results The prevalence of biopsy-proven diabetic nephropathy (DN) has increased significantly from 2.5% to 6.0% in the total cohort in the recent 30 years with an increase in the prevalence of diabetes. Approximately 68% of total diabetic patients had non-diabetic renal disease (NDRD); the proportion was retained since 2000s. DN showed a significantly higher risk of ESKD than NDRD (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.35 to 1.88). The prevalence of biopsy-proven HT-N remained < 2% in the total cohort for several decades. There was no difference in risks of ESKD between patients with or without biopsy-proven HT-N (HR, 0.93; 95% CI, 0.54 to 1.59). Conclusions In recent decades, the prevalence of diabetes and DN has significantly increased in the kidney biopsy cohort, showing an increased risk of ESKD. Despite the large numbers of patients meeting the clinical criteria of HT-N, most of those were diagnosed with pathologic diagnoses other than HT-N.

Modern concepts about the role of connective tissue growth factor in various physiological and pathological processes are described in the review. Connective tissue growth factor regulates a variety of cellular functions, including proliferation, migration, adhesion, differentiation and synthesis of extracellular matrix proteins in cells of different types. This factor is also involved in more complex biological processes of angiogenesis, chondrogenesis, wound healing, fibrosis and oncogenesis. Increased expression of connective tissue growth factor is observed in different cardiovascular and oncological diseases. Potential role of this growth factor in regulation of cellular senescence and aging processes is also discussed.

Background: The medium‐ to long‐term outcomes of living kidney donors with hypertension compared to normotensive donors are not well understood, especially with the recent changes in hypertension guidelines. Methods: We studied a cohort of 950 living kidney donors using different definitions of hypertension based on either ≥140/90 or ≥130/80 mmHg thresholds and based on either office or ambulatory blood pressure readings. Microstructural features on kidney biopsy at the time of donation were compared using different definitions of hypertension. Results: After adjusting for years of follow‐up, age, sex, and baseline eGFR, hypertension (by any definition) did not significantly predict an eGFR < 45 ml/min/1.73 m2 at a median follow‐up of 10 years postdonation, though there was a borderline association with ambulatory blood pressure ≥ 130/80 mmHg predicting a 40% decline in eGFR (OR = 1.53, 1.00–2.36; p =.051). Proteinuria was predicted by office blood pressure ≥ 140/90 mmHg and by nondipper profile on nocturnal ambulatory blood pressure measurements. At the time of donation, larger glomeruli and arterial hyalinosis on biopsy were associated with hypertension defined by either ≥140/90 or ≥130/80 mmHg (by office or ambulatory measurements). Nocturnal nondipper status was associated with larger glomeruli size but not arteriolar hyalinosis when compared to dippers. Conclusions: In programs that accept donors with controlled hypertension, various definitions of hypertension are associated with histological findings in the donated kidney, but none predict a clinically significant decline in kidney function 10 years after donation. These data support allowing healthy individuals with controlled hypertension to donate a kidney. However, donors with office hypertension (≥140/90 mmHg) and nondippers (regardless of hypertension status) are at greater long‐term risk for proteinuria, and particularly for these donors, longer follow‐up is warranted. [ABSTRACT FROM AUTHOR]

Background: Hypertensive nephrosclerosis is the presumed underlying cause in many end‐stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy. Objective: To evaluate and improve the diagnostic process for nephrosclerosis patients. Methods: We included adults from the population‐based HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988–2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve‐based methods of optimal cut‐offs were used to improve clinical nephrosclerosis criteria. Results: Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney‐related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy‐verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (<0.75 g d−1), systolic blood pressure (>155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false‐positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk‐tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy. Conclusion: Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Some living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes., Study Design: Retrospective cohort study., Setting & Participants: Single center, living donor kidney transplants from January 2010 to July 2022., Exposure: Chronic histological changes, glomerular disease in donor kidney implantation biopsies., Outcome: For donors, single-kidney estimated glomerular filtration rate (eGFR) increase, percent total eGFR loss, ≥40% eGFR decline from predonation baseline, and eGFR<60mL/min/1.73m 2 at 6 months after donation; for recipients, death-censored allograft survival., Analytical Approach: Biopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes., Results: Among 1,104 living donor kidneys, 155 (14%) had advanced chronic changes on implantation biopsy, and 12 (1%) had findings suggestive of possible donor glomerular disease. Adjusted logistic regression showed that age (odds ratio [OR], 2.44 per 10 years [95% CI, 1.98-3.01), Hispanic ethnicity (OR, 1.87 [95% CI, 1.15-3.05), and hypertension (OR, 1.92 [95% CI, 1.01-3.64), were associated with higher odds of chronic changes on implantation biopsy. Adjusted linear regression showed no association of advanced chronic changes with single-kidney eGFR increase or relative risk of eGFR<60mL/min/1.73m 2 . There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities., Limitations: Retrospective, absence of measured GFR., Conclusions: Approximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival., Plain-Language Summary: Kidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 30-UTR. In chromaffin cell-transfected CHGA 30-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 30-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 30-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects.

Grafted kidney abnormalities include a wide spectrum of diseases that differ in their nature, mechanisms of development, and rates of progression. In the early period after renal transplantation, the most important cause of graft dysfunction remains to be acute rejection that results from a recipient's immunological response to a donor's transplantation antigens and develops with the activation of both cellular and humural immune responses. In the late periods, one of the main causes of late graft losses is chronic graft dysfunction, the morphological substrate of which is progressive nephrosclerosis. The development of graft nephrosclerosis is generally associated with the combined effects of a large variety of both immune and nonspecific factors; however, the morphological features make it possible to identify the preponderance of this or that mechanism in its origin and, in this connection, individual nosological entities. The latter include chronic rejection, calcineurin inhibitorinduced nephrotoxicity, and nephrosclerosis caused by rejection-unassociated conditions, such as ischemic-reperfusion lesion, obstructive nephropathy, viral graft damage, etc. Moreover, as more time elapses after renal allotransplantation (RAT), there is a higher incidence of recurrent and de novo diseases, the most common types of which are IgA-nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, etc. Puncture biopsy using immunofluorescence and electron microscopy is the gold standard of the diagnosis of graft kidney abnormalities since only the morphological verification of the diagnosis permits adequate immunosuppressive therapy, by improving the long-term results of RAT. The paper presents diagnostic criteria and morphological features of different types of renal graft diseases.

Ageing of the kidney is a multi-dimensional process that occurs simultaneously at the molecular, cellular, histological, anatomical and physiological level. Nephron number and renal cortical volume decline, renal tubules become atrophic and glomeruli become sclerotic with age. These structural changes are accompanied by a decline in glomerular filtration rate, decreased sodium reabsorption and potassium excretion, reduced urinary concentrating capacity and alterations in the endocrine activity of the kidney. However, the pace of progression of these changes is not identical in everyone - individuals of the same age and seemingly similar clinical profile often exhibit stark differences in the age-related decline in renal health. Thus, chronological age poorly reflects the time-dependent changes that occur in the kidney. An ideal measure of renal vitality is biological kidney age – a measure of the age-related changes in physiological function. Replacing chronological age with biological age could provide numerous clinical benefits including improved prognostic accuracy in renal transplantation, better stratification of risk and identification of those who are on a fast trajectory to an age-related drop in kidney health.

The relationship of APOL1 renal risk variants to cardiovascular disease (CVD) is controversial and was the subject of this investigation. Methods: Age, cause of death, and nephrosclerosis (the latter defined by glomerulosclerosis) were analyzed in the autopsies of 162 African Americans and 136 whites genotyped for APOL1 risk alleles. Results: Sudden deaths represented >75% of CVD autopsies for both races and all-risk genotypes. The average ages of CVD deaths for African Americans with 1 and 2 APOL1 risk alleles were, respectively, 7.0 years (P = 0.02) and 12.2 years (P < 0.01) younger than African Americans with 0 risk alleles and 8.7 years (P = 0.01) and 13.9 years (P = 0.01) younger than whites. Age differences were not significant between African Americans and whites with 0 risk alleles (P = 0.61). The younger CVD deaths of African Americans were associated with less severe glomerulosclerosis with 2 (P = 0.01), although not 1 (P = 0.09), compared with 0 APOL1 risk alleles. Cardiomyopathy was found in 23% of African Americans with 1 and 2 risk alleles and significantly contributed to the lower age (P = 0.01). For non-CVD deaths, age differences were not seen by race (P = 0.28) or among African Americans by risk allele status (P = 0.38). Conclusion: Carriage of 1 or 2 APOL1 risk alleles in African Americans was associated with earlier age deaths due to coronary artery disease and cardiomyopathy. For 2 risk alleles, the early age was independent of nephrosclerosis.

Background: Systemic diseases, diabetes mellitus (DM), and cardiovascular disease (CaVD) have been suggested being risk factors for cognitive impairment (CI) and/or influence Alzheimer's disease neuropathologic change (ADNC).Objective: The purpose was to assess the type and the extent of neuropathological alterations in the brain and to assess whether brain pathology was associated with CaVD or DM related alterations in peripheral organs, i.e., vessels, heart, and kidney.Methods: 119 subjects, 15% with DM and 24% with CI, age range 80 to 89 years, were chosen and neuropathological alterations were assessed applying immunohistochemistry.Results: Hyperphosphorylated τ (HPτ) was seen in 99%, amyloid-β (Aβ) in 71%, transactive DNA binding protein 43 (TDP43) in 62%, and α-synuclein (αS) in 21% of the subjects. Primary age related tauopathy was diagnosed in 29% (more common in females), limbic predominant age-related TDP encephalopathy in 4% (14% of subjects with CI), and dementia with Lewy bodies in 3% (14% of subjects with CI) of the subjects. High/intermediate level of ADNC was seen in 47% and the extent of HPτ increased with age. The extent of ADNC was not associated with the extent of pathology observed in peripheral organs, i.e., DM or CaVD. Contrary, brain alterations such as pTDP43 and cerebrovascular lesions (CeVL) were influenced by DM, and CeVL correlated significantly with the extent of vessel pathology.Conclusion: In most (66%) subjects with CI, the cause of impairment was "mixed pathology", i.e., ADNC combined with TDP43, αS, or vascular brain lesions. Furthermore, our results suggest that systemic diseases, DM and CaVD, are risk factors for CI but not related to ADNC. [ABSTRACT FROM AUTHOR]

Background: Hypertension is prevalent in 35%--46% of the general population; 1% of them experience accelerated hypertension. Among patients with accelerated hypertension, acute worsening of renal functions occur in 22%-55%. Morbidity and mortality rates are high. Partial renal recovery is seen in some, while others rapidly progress to end-stage renal disease. Methods: Patients who presented with accelerated hypertension, renal dysfunction, and had undergone renal biopsy were evaluated and their clinical profile was analyzed. Those who became dialysis dependent were excluded from further follow-up. Study outcome were blood pressure control, renal functions, requirement of renal replacement and mortality. Results: Of the 30 patients evaluated, age at presentation was 41.2 ± 15.46 years and 26 (86.7%) were males, 10 (33%) had presented with nonspecific complaints. Mean duration of hypertension and blood pressure were 21.93 months and 196 ± 20.8/129 ± 12.4 mmHg, respectively. Glomerulonephritis and hypertensive nephrosclerosis had similar characteristics except proteinuria (P = 0.04). Average follow-up (n = 25) duration was 3.69 years (range: 0.05--9.6). At the end of study, 6 were dialysis dependent, while in others, mean e-GFR was 23.96 ml/min/1.73 m². Poor renal prognosis was predicted by glomerulonephritis (relative risk-4.6) and degree of interstitial fibrosis. Five-year patient and renal survival were 94.4% and 71.9%, respectively. Conclusion: Accelerated hypertension occurs among patients with both primary and secondary hypertension. It leaves permanent renal sequelae. Though some patients recover renal function partially, further progression is rapid, especially among those with chronic glomerulonephritis. [ABSTRACT FROM AUTHOR]

In the 2017 Annual Report of the ERA-EDTA Registry, hypertension continues to be the second or third most common cause of renal replacement therapy (RRT) in Europe, tied with glomerulonephritis. There is, however, one little issue: hypertension-induced end-stage renal disease (ESRD) might not exist at all as currently understood, that is, as hypertensive nephrosclerosis. In this regard, the incidence of RRT due to hypertensive nephropathy is related to the incidence of other causes of ESRD but not to the burden of hypertension per country. The current definition of hypertensive nephropathy is non-specific, outdated and only allows a delayed diagnosis by exclusion. It is not helpful that 80% of chronic kidney disease patients develop hypertension and kidney biopsy has no findings specific for hypertensive nephropathy. There is an urgent need to redefine the concept of hypertensive nephropathy with a clear and comprehensive set of criteria that at least should indicate how other nephropathies, including familial nephropathies, should be excluded. Correct causality assessment and aetiology-based therapy is a key to the progress of nephrology and it should no longer be accepted that 'hypertensive nephropathy' serves to disguise a suboptimal diagnostic workup. A diagnosis of nephropathy of unknown cause would be more honest when the full range of alternative aetiological diagnoses is not explored. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the urinary levels of TGF-β1, VEGF, and MCP-1 as potential biomarkers of latent inflammation and fibrosis in the kidney before and 6 months after correction of vesicoureteral reflux (VUR) in children. Methods: A total of 88 patients (mean age 26 months) with VUR were divided into three groups: group A—patients with grades II–III VUR, conservative treatment; group B—patients with grades III–V VUR, endoscopic correction of VUR; group C—patients with grades III–V VUR, ureteral reimplantation after failed endoscopic correction. Control group included 20 healthy children. Biomarker levels were measured by ELISA. 99mTc-DMSA scintigraphy and renal histology were performed if possible. Results: At admission, TGF-β1 was close to control in all study groups, VEGF increased with severity of the disease, and MCP-1 increased in group C. Six months after correction of VUR, despite clinical and laboratory improvement, TGF-β1 and MCP-1 increased while VEGF decreased compared to the admission values in all groups; no amelioration of renal scarring was detected either by 99mTc-DMSA scintigraphy or renal histology. Conclusion: The results support our hypothesis that successful correction of VUR is not sufficient to stop or reduce the latent inflammatory and fibrotic processes that have already started in the kidney regardless of the reflux grade and treatment option. Measuring the urinary levels of TGF-β1, VEGF, and MCP-1 may aid in the development of non-invasive, pathophysiologically relevant approach to diagnosis and monitoring of kidney injury and fibrosis in children with VUR. [ABSTRACT FROM AUTHOR]

Hypertensive nephrosclerosis is the second most common cause of end-stage renal disease after diabetes. For years, hypertensive kidney disease has been focused on the afferent arterioles and glomeruli damage and the involvement of the renin angiotensin system (RAS). Nonetheless, in recent years, novel evidence has demonstrated that persistent high blood pressure injures tubular cells, leading to epithelial–mesenchymal transition (EMT) and tubulointerstitial fibrosis. Injury primarily determined at the glomerular level by hypertension causes changes in post-glomerular peritubular capillaries that in turn induce endothelial damage and hypoxia. Microvasculature dysfunction, by inducing hypoxic environment, triggers inflammation, EMT with epithelial cells dedifferentiation and fibrosis. Hypertensive kidney disease also includes podocyte effacement and loss, leading to disruption of the filtration barrier. This review highlights the molecular mechanisms and histologic aspects involved in the pathophysiology of hypertensive kidney disease incorporating knowledge about EMT and tubulointerstitial fibrosis. The role of the Hsp70 chaperone on the angiotensin II–induced EMT after angiotensin II type 1 receptor (AT1R) blockage, as a possible molecular target for therapeutic strategy against hypertensive renal damage is discussed.

Pheochromocytomas are neuroendocrine tumors derived from embryonic neural crest cells. They are mostly found in the adrenal glands (pheochromocytomas) and sometimes in the extra-adrenal paraganglia (paragangliomas) of the autonomic nervous system. Paragangliomas arising from the kidney or in the renal hilus are very rare, and preoperative diagnosis is rarely made.We present the case of a 38-year-old hypertensive female, presenting with dull aching, nonradiating right flank pain for 2 months and no other symptoms. Computed tomography demonstrated a well-defined, hypodense enhanced lesion located on the hilum of the right kidney. Laparotomy was performed, and histology of the excised mass revealed an extra-adrenal pheochromocytoma. The intervention was effective, and the patient is doing fine.

A high prevalence of chronic kidney disease (CKD) occurs in patients with myeloproliferative neoplasms (MPN). However, MPN-related glomerulopathy (MPN-RG) may not account for the entirety of CKD risk in this population. The systemic vasculopathy encountered in these patients raises the hypothesis that vascular nephrosclerosis may be a common pattern of injury in patients with MPN and with CKD. In an exhaustive, retrospective, multicenter study of MPN kidney biopsies in four different pathology departments, we now describe glomerular and vascular lesions and establish clinicopathologic correlations. Our study encompassed 47 patients with MPN who underwent a kidney biopsy that included 16 patients with chronic myeloid leukemia (CML) and 31 patients with non-CML MPN. Fourteen cases met a proposed definition of MPN-RG based on mesangial sclerosis and hypercellularity, as well as glomerular thrombotic microangiopathy. MPN-RG was significantly associated with both myelofibrosis and poorer kidney survival. Thirty-three patients had moderate-to-severe arteriosclerosis while 39 patients had moderate-to-severe arteriolar hyalinosis. Multivariable models that included 188 adult native kidney biopsies as controls revealed an association between MPN and chronic kidney vascular damage, which was independent of established risk factors such as age, diabetes mellitus and hypertension. Therefore, MPN-RG is associated with myelofibrosis and has a poor kidney prognosis. Thus, our findings suggest that the kidney vasculature is a target during MPN-associated vasculopathy and establish a new link between MPN and CKD. Hence, these results may raise new hypotheses regarding the pathophysiology of vascular nephrosclerosis in the general population., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Diabetes and hypertension share renal histopathological features, such as arterial lesions and glomerular hypertrophy, that have not been investigated in relation to the blood pressure status of diabetic subjects. The severity of glomerular lesions varies across locations of the renal cortex, which may be further affected by diabetes and/or hypertension. METHODS Histopathological lesions in different parts of the renal cortex of autopsy kidneys were evaluated and analyzed based on medical histories of diabetes and hypertension. RESULTS This study included a total of 82 Japanese autopsies composed of normotensive nondiabetics (n = 31), hypertensive nondiabetics (n = 28), normotensive diabetics (n = 14), and hypertensive diabetics (n = 9). There were no differences in age, sex, renal function, or body size among groups. In both the superficial and juxtamedullary cortices, increased glomerular volume (GV) was significantly associated with either diabetes or hypertension. In addition, diabetes and hypertension showed a significant interaction with GV regardless of the cortical location. Values for global glomerulosclerosis (GGS) and arteriolar hyalinosis (AH) were associated with diabetes but not with hypertension. Only values for GGS consistently showed cortical surface superiority. The zonal distribution of AH, GV, or other diabetic glomerular lesions differed among the lesions depending on the presence or absence of hypertension. CONCLUSIONS These results imply that diabetes and hypertension synergistically enhance glomerular hypertrophy across all layers of the human renal cortex. The process is closely associated with the severity of GGS and AH predominantly associated with diabetes. [ABSTRACT FROM AUTHOR]

Background Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. Methods We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by  ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. Results During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35–0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54–0.94), eGFR (SHR 0.98; 95% CI 0.97–0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08–1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00–1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20–1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. Conclusions The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis. [ABSTRACT FROM AUTHOR]

The article highlights a study of Sclerotic Renal Histopathological Lesions in Adults With Normal Renal Function. Topics include Arterial hypertension and glomerular ischemia coexist in elderly patients with hypertension and adult autopsied kidneys without apparent renal disease were analyzed for histopathological features that might be related to aging or hypertension; and concludes that normal aging has a major impact on the development of renal sclerotic lesions.