The Renal Resistive Index in Allografts: Is Sonographic Assessment Sufficiently Reproducible in a Routine Clinical Setting? - Reproducibility of the Renal Resistive Index.

PURPOSE: To assess the reproducibility of the renal resistive index (RRI) in a routine clinical setting. MATERIALS AND METHODS: 22 patients with a kidney allograft and 19 physicians participated in our prospective study. Within 2 hours each patient was examined by 5 different physicians using 2 out of 3 different, randomly allocated ultrasound machines. Each investigator determined the hilar and parenchymal RRI of the allograft. The reproducibility and reproducibility limit of the RRI were assessed as well as Cronbach's alpha and the intraclass correlation coefficient (ICC). The deviation of the RRI from the mean RRI over the 5 measurements was used as an indicator of reproducibility. The impact of the ultrasound machine, examiner's level of experience, and kidney function impairment (GFR < 45 ml/min) was assessed with the Kruskal-Wallis test. The bivariate linear correlation of the minimal transplant distance from the body surface with the variance of the parenchymal RRI was analyzed. RESULTS: A reproducibility of 0.045 with a reproducibility limit of 0.124 was found for the parenchymal RRI. The ICC between RRIs was good with 0.852 for the parenchymal RRI and 0.868 for the hilar RRI. The type of ultrasound machine used was found to have a significant impact on the deviation of the parenchymal RRI (Kruskal-Wallis-Test, p = 0.003). Variance in serial parenchymal RRI measurements correlated significantly with the depth of the kidney transplant (p = 0.001). CONCLUSION: While the RRI is generally sufficiently reproducible, the type of ultrasound machine used and the depth of the kidney transplant within the recipient's body have a significant impact on reproducibility. KEY POINTS: · The renal resistive index (RRI) in allografts is reproducible.. · The type of ultrasound machine has an impact on the measured RRI.. · RRI reproducibility decreases with the depth of the renal allograft in the recipient.. CITATION FORMAT: · Theilig DC, Münzfeld H, Auer TA et al. The Renal Resistive Index in Allografts: Is Sonographic Assessment Sufficiently Reproducible in a Routine Clinical Setting?. Fortschr Röntgenstr 2020; 192: 561 - 566.

Glomerular Endothelial Cells: Assessment of Barrier Properties In Vitro.

Endothelial cells form the inner lining of all blood vessels and play a vital role in regulating vascular permeability. This applies to the circulation in general and also to specific capillary beds including the renal glomerular capillaries. Endothelial dysfunction, including increased permeability, is a key component of diabetes-induced organ damage. Endothelial cells together with their glycocalyx, grown on porous membranes, provide an excellent model to study endothelial permeability properties. Here we describe the measurement of two characteristics of glomerular endothelial cell (GEnC) monolayers: electrical resistance and macromolecular passage. Trans-endothelial electrical resistance provides a measure of small-pore pathways across the endothelium and provides an index of monolayer confluence and cell-cell junction integrity. Measurement of macromolecular passage provides an index of large-pore pathways and use of labeled albumin provides direct relevance to the clinically important parameter of albuminuria. The combination of the two approaches provides a fantastic tool to elucidate endothelial barrier function in vitro including in response to cytokines, pathological stimuli, and potential therapeutic agents.

Diagnostic significance of peritubular capillary basement membrane multilaminations in kidney allografts: old concepts revisited.

BACKGROUND: Injury to peritubular capillaries and capillary basement membrane multilamination (PTCL) is a hallmark of antibody-mediated chronic renal allograft rejection. However, the predictive diagnostic value of PTCL is incompletely studied. METHODS: We analyzed the diagnostic significance of PTCL and propose diagnostic strategies. We evaluated 360 diagnostic native and 187 transplant kidney specimens by electron microscopy (terminology: PTCL-C, severe; PTCL subgroup C3, very severe multilamination; see Materials and Methods for definitions). RESULTS: PTCL was not pathognomonic for any specific disease. PTCL-C/C3 was rare in native kidneys (C, 6%; C3, 1%), associated mainly with late thrombotic microangiopathy (C: 78%; C3: 11% of cases). In allografts, PTCL-C/C3 was significantly more common, especially in specimens more than 24 months after transplantation (C, 47%; C3, 31%). PTCL-C/C3 was found in acute (C, 20%; C3, 7%) and chronic T-cell rejection (C, 67%; C3, 29%), calcineurin inhibitor toxicity (C, 36%; C3, 18%), or C4d(+) specimens (C, 61%; C3, 50%) with odds ratios between 4 and 36. PTCL-C3 was more predominant in cases with antibody-mediated injury. Highest odds ratios (81-117) for PTCL-C/C3 were noted in combined injuries, that is, mixed chronic T-cell and concurrent chronic antibody-mediated rejection. Positive predictive values of PTCL-C and C3 are the following: all rejection types, 89% and 93%; all Banff chronic rejection types, 69% and 71%; and chronic presumptive antibody rejection, 37% and 49%, respectively. Corresponding negative predictive values of C and C3 for different Banff rejection categories are between 50% and 94%. CONCLUSIONS: The presence of PTCL-C3 is a helpful adjunct finding to diagnose rejection-induced tissue injury but cannot precisely predict the Banff rejection category. Conversely, the absence of PTCL-C3 is helpful in excluding chronic, Banff category II antibody-mediated rejection.

Prospective assessment of C4d deposits on circulating cells and renal tissues in lupus nephritis: a pilot study.

Complement activation plays a key role in the pathogenesis of lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE). We prospectively evaluated 15 LN subjects and two control groups: 13 non-SLE renal subjects (control A) and 239 SLE subjects without LN (control B). All had C4d levels on circulating erythrocytes (E-C4d), reticulocytes (R-C4d) and platelets (P-C4d) measured by flow cytometry, while C4d deposition in renal tissue was semiquantitatively assessed in LN subjects and control A using immunoperoxidase staining. Compared with control A, LN biopsies had higher glomerular-C4d scores (p = 0.003), which were associated with more frequent granular glomerular immunofluorescence staining and electron dense deposits (p < 0.001). Compared with control A and B groups, LN subjects had higher E-C4d (p = 0.002 and p = 0.005) and R-C4d levels (p = 0.002 and p = 0.008), respectively. LN subjects were more likely to have P-C4d compared with control A (p = 0.016). In LN, only E-C4d correlated with National Institutes of Health (NIH) activity index (r = 0.55, p = 0.04). In conclusion, LN biopsies showed frequent glomerular-C4d staining associated with immune complex deposits. LN subjects had higher E-C4d and R-C4d levels compared with both control groups. E-C4d levels also correlated with NIH activity index. These findings suggest a potential role of C4d on circulating cells as a biomarker for lupus nephritis.

Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, p<.001). Values for the glomerular pressure and the resistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

Indirect assessment of glomerular capillary pressure from pressure-natriuresis relationship: comparison with direct measurements reported in rats.

It is examined whether glomerular hemodynamics can be indirectly estimated from the pressure-natriuresis relationship. There are only two animal studies reported, one in normal and the other in 5/6 nephrectomized Munick-Wistar rats, which permits plotting the pressure-natriuresis relationship and comparison of indirect estimations with directly measured glomerular hemodynamic data. Normal and extensive renal ablation rats were placed on relatively high and low sodium diets. Plotting mean arterial pressure (MAP) on the x-axis and 24 h urinary sodium excretion rate on the y-axis, the pressure-natriuresis relationship was drawn. As the difference between MAP (121 +/- 1 and 169 +/- 12 mmHg) on relatively high sodium diet and the extrapolated x-intercept (122 and 138 mmHg) of the pressure-natriuresis relationship, based on previous proposal, the effective filtration pressure across the glomerular capillary walls was estimated to be-1 and 31 mmHg for normal and 5/6 nephrectomized rats. Then, the glomerular capillary hydraulic pressure (PGC) was calculated to be 33 and 64 mmHg. Micropuncture studies showed that directly measured PGC of 47 +/- 1 and 65 +/- 2 mmHg was close agreement with those estimated indirectly. Therefore, an approach from the pressure-natriuresis relationship provides a noninvasive means to predict an approximation of PGC. This approach to estimating glomerular hemodynamics may have invaluable implications for clinical practice; in the early detection of loss of filtration capacity and in the assessment of an important risk factor for the development of chronic renal failure.

Role of postglomerular microvessels in pathophysiology of diabetic nephropathy. Assessment and hypothesis.

Although glomerular damage plays a well-established and important role in the pathomechanism of diabetic nephropathy, it alone does not fully explain the progression of renal complications in long-term diabetes mellitus. We discuss experimental evidence showing involvement of the postglomerular microvessels (peritubular capillaries and venules) in diabetic microangiopathy. This involvement is manifest in increased permeability of these vessels to plasma proteins and in highly augmented lymphatic drainage of the extravasated proteins from the renal interstitium. We suggest that in the advanced phase of diabetic nephropathy, proteinuria (corresponding to excess leakage of proteins through the glomerular capillary wall) indicates the probability that postglomerular microvessels have also allowed leakage of plasma proteins. As long as lymphatic drainage is capable of removing the increased quantity of extravasated plasma proteins from the interstitium, renal function should not be deleteriously affected. However, if the excess amount of extravasated proteins exceeds the capacity of lymphatic drainage, increases in interstitial volume and pressure are unavoidable with detrimental consequences for glomerular filtration and tubular reabsorption. Under these conditions, a potential positive-feedback loop can be visualized that involves increased extravasation of plasma proteins leading to increased interstitial pressure that through dilation of the afferent and efferent arterioles results in a further increase in protein extravasation. These conditions combined with glomerular damage should lead to the eventual collapse of renal function.