The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney. Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson’s correlation coefficient and linear regression were used to assess relations between parameters.Results: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 μm2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.β = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.β = 0.31, p = 0.01) and at five years (St.β = 0.30, p = 0.01) after donation, independent of age.Conclusions: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors. Graphical abstract: [Figure not available: see fulltext.]</p

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Interobserver agreement of scoring of histopathological characteristics and classification of lupus nephritis.

Contains fulltext : 69663.pdf (publisher's version ) (Open Access)BACKGROUND: Assessing renal biopsies from patients with lupus nephritis (LN) is a difficult task and it is subject to interobserver variability. In this study the interobserver agreement amongst five nephropathologists was analysed. METHODS: Five specialized nephropathologists scored 126 biopsies, comprising 87 first and 39 repeat biopsies from 87 patients with biopsy-proven proliferative LN, included in a randomized controlled trial. The interobserver agreement [expressed as intraclass correlation coefficients (ICC)] of the scored histopathological items was calculated. Also, the WHO1995 and ISN/RPS2003 classification systems for LN were compared, with extra attention being given to the comparison between patients with diffuse proliferative LN with either segmental (IV-S) or global (IV-G) lesions. RESULTS: There was a wide range of agreement. A good interobserver agreement (ICC>0.6) was present in 15%, and a moderate interobserver agreement (ICC 0.4-0.6) in 31% of the scored items. The activity index for LN showed a good (ICC 0.716) and the chronicity index a moderate (ICC 0.494) interobserver agreement. Both classification systems showed low agreement, although consensus was easily reached. Patients classified as IV-S (n=15) had more favorable clinical parameters at study entry than those with class IV-G (n=57). Although suggested by others, we found no differences in outcome between these two subclasses. CONCLUSIONS: This study shows that, although definitions were agreed upon beforehand, even specialized on nephropathologists have difficulties with scoring histopathological characteristics of LN, particularly with SLE the classification systems

Prematurity, perinatal inflammatory stress, and the predisposition to develop chronic kidney disease beyond oligonephropathy

Prematurity and perinatal stress, such as intrauterine growth restriction (IUGR) and chorioamnionitis, are pathological processes creating an impaired intrauterine environment. These intrauterine factors are associated with the development of proteinuria, hypertension, and chronic kidney disease (CKD) later in life. Initially, this was thought to be secondary to oligonephropathy, subsequent glomerular hypertrophy, and hyperfiltration, leading to glomerulosclerosis, a further decrease in nephron number, and finally CKD. Nowadays, there is increasing evidence that prematurity and perinatal stress affect not only nephron endowment but also the maturation of podocytes and vasculogenesis. IUGR is associated with podocyte damage and an aggravated course of nephrotic syndrome. Moreover, preterm birth and IUGR are known to cause upregulation of the postnatal renin-angiotensin system, resulting in hypertension. Chorioamnionitis causes damage to the glomeruli, thereby predisposing to the development of glomerulosclerosis. This review aims to summarize current knowledge on the influence of prematurity, IUGR, and chorioamnionitis on the development of different glomerular structures. After summarizing human and experimental data on low nephron number in general, a specific focus on the current understanding of podocyte and glomerular capillary formation in relation to prematurity and different causes of perinatal stress is presented

Morphological MRI criteria improve the detection of lymph node metastases in head and neck squamous cell carcinoma: multivariate logistic regression analysis of MRI features of cervical lymph nodes

The aim was to evaluate whether morphological criteria in addition to the size criterion results in better diagnostic performance of MRI for the detection of cervical lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). Two radiologists evaluated 44 consecutive patients in which lymph node characteristics were assessed with histopathological correlation as gold standard. Assessed criteria were the short axial diameter and morphological criteria such as border irregularity and homogeneity of signal intensity on T2-weighted and contrast-enhanced T1-weighted images. Multivariate logistic regression analysis was performed: diagnostic odds ratios (DOR) with 95% confidence intervals (95% CI) and areas under the curve (AUCs) of receiver-operating characteristic (ROC) curves were determined. Border irregularity and heterogeneity of signal intensity on T-2-weighted images showed significantly increased DORs. AUCs increased from 0.67 (95% CI: 0.61-0.73) using size only to 0.81 (95% CI: 0.75-0.87) using all four criteria for observer 1 and from 0.68 (95% CI: 0.62-0.74) to 0.96 (95% CI: 0.94-0.98) for observer 2 (p < 0.001). This study demonstrated that the morphological criteria border irregularity and heterogeneity of signal intensity on T2-weighted images in addition to size significantly improved the detection of cervical lymph nodes metastases