Tissue Expression of Aquaporin 2 Is Correlated to Urine Output and Allograft Function in Sensitized Kidney Transplant Patients.

BACKGROUND: Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. METHODS: Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68). The indication biopsy specimens were further divided into 3 subgroups according to the presence of acute tubular necrosis or rejection. Normal kidney tissue samples (n = 6) served as the control specimens. Immmunohistochemical expression of AQP1, AQP2, and ENAC was determined by using image analyzing software. RESULTS: Significantly lower AQP1 expression was observed in the time-zero and indication biopsy specimens with rejection compared with control specimens (P = .03 and P = .04, respectively). AQP2 expression was significantly lower in patients with an indication biopsy specimen compared with control and protocol biopsy specimens (P = .05 and P = .005). For ENAC, a lower expression was noted in the indication biopsy specimens compared with the control specimens (P = .04). Both AQP1 and AQP2 tissue expressions were significantly correlated to urine output (r = 0.45 and r = 0.32; P = .001 and P = .02), and AQP2 was correlated with the glomerular filtration rate estimated by using the Modification of Diet in Renal Disease Study equation at biopsy (r = 0.23; P = .05). CONCLUSIONS: These findings partially confirm previous experimental data showing downregulation of AQP1 expression after ischemia/reperfusion injury and during rejection. AQP2 downregulation seems to be rejection-independent, occurring during deteriorating or poor kidney graft function.

Renal Artery Stenosis - are there Patients who Benefit from Intervention?

Atherosclerotic renal artery stenosis (ARAS) is one of the most relevant long-term complications of atherosclerotic disease. It is associated both with hypertension and increased renal and cardiovascular risk and overall mortality. Diagnostic modalities include non-invasive duplex ultrasound, dynamic magnetic resonance angiography (MRA) and computer tomography angiography (CTA) and are confirmed by using invasive renal angiography. Percutaneous revascularization of renal artery stenosis has been studied in various clinical trials. With regard to hypertension, several case series could show a clinical response to revascularization. However, the majority of randomized clinical trials could not confirm the correlation between intervention and the improvement of hypertension, kidney function, cardiovascular events, and mortality. Based on this predication the crucial tool in the treatment of ARAS is an optimal medical therapy, including statins, antihypertensive agents and platelet inhibition. Today the core point is to select subgroups and appropriate indications for better outcomes and avoiding unnecessary procedures very carefully. Therefore in patients with typical manifestations of ARAS including resistant or malignant hypertension, progressive decline of renal function, flash pulmonary edema or angina, renal artery intervention remains a sensible therapeutic option - after hemodynamic testing prior to revascularization. In the future further trials targeting patients who fulfill rational selection criteria need to be undertaken to confirm the efficacy of revascularization.

Contrast-enhanced ultrasonography in the early period after kidney transplantation predicts long-term allograft function.

INTRODUCTION: Real-time contrast-enhanced sonography (CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The purpose of the study was to evaluate the feasibility of early CES in predicting long-term kidney allograft function in comparison to color Doppler ultrasonography (CDUS). METHODS: We prospectively studied 68 consecutive kidney transplant recipients using CES and conventional CDUS investigation 1 week after transplantation. Transplant tissue perfusion imaging was performed by low-power imaging during intravenous administration of the sonocontrast SonoVue. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow (RBF). The obtained sonography values were correlated with clinical data 1 week up to 1 year after transplantation. RESULTS: In contrast with conventional CDUS resistive indices, RBF estimated by CES 1 week posttransplantation significantly correlated with kidney function after 1 year (r = 0.67; P < .001). Determination of RBF by CES revealed a significant correlation with donor age but not recipient age, whereas conventional CDUS resistive index was significantly correlated to recipient age (r = 0.54; P < .001) but not donor age. Furthermore RBF was associated with vascular fibrosis and intimal thickening of the engraftment biopsies. CONCLUSION: This is the first prospective study demonstrating the prognostic value of CES early after kidney transplantation. In contrast with CDUS, CES reveals information about kidney allograft perfusion independent of recipient vascular compliance.

Glucose effects on the peritoneum: what can we learn from rodent models?

During long-term peritoneal dialysis (PD) the peritoneal membrane underlies processes of structural and functional reorganization mediated by high glucose and reactive glucose metabolites that are contained in PD solutions; this process is accompanied by increasing fibrosis. Mechanistically, the peritoneal damage is triggered by the interaction of advanced glycation end-products with their receptor; this is true for rodents as well as for humans. With this knowledge interventional strategies can be tested in rodent models, among them are the lipid soluble vitamin B1 analogue benfotiamine (BF) or detoxifying enzymes such as glyoxalase. Of additional interest is the finding that PD fluids do not only cause local but also systemic damage, in particular renal and cardiovascular. In the case of kidney damage, the intervention with BF was also successful. Taken together, PD can be regarded as a local model for long-term diabetes together with systemic aspects of damage.

Immunosuppression after kidney transplantation.

Today kidney transplantation features excellent short-term outcomes with decreasing acute rejection episodes. In contrast, improvement of long-term allograft survival is much less impressive over the last decades. Thus, the goal of current immunosuppressive therapies is keeping the balance between the reduction of acute rejection episodes and organ specific and systemic side effects. With the development of a broad armamentarium of new immunosuppressive agents with different mechanisms of action, the minimization or avoidance of corticosteroids and calcineurin inhibitors became feasible.

Renal toxicity mediated by glucose degradation products in a rat model of advanced renal failure.

BACKGROUND: In peritoneal dialysis (PD) residual renal function contributes to improved patient survival and quality of life. Glucose degradation products (GDP) generated by heat sterilization of PD fluids do not only impair the peritoneal membrane, but also appear in the systemic circulation with the potential for organ toxicity. Here we show that in a rat model of advanced renal failure, GDP affect the structure and function of the remnant kidney. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned to a two stage subtotal nephrectomy (SNX) or sham operation and were left untreated for 3 weeks. The SNX + GDP group continuously received chemically defined GDP intravenously for 4 weeks; the SNX and the sham-operated rats remained without GDP. The complete follow-up for all groups was 7 weeks postoperatively. We analysed renal damage using urinary albumin excretion as well as a semiquantitative score for glomerulosclerosis and tubulointerstitial damage, as well as for immunohistochemical analyses. RESULTS: The SNX + GDP rats developed significantly more albuminuria and showed a significantly higher score of glomerulosclerosis index (GSI) and tubulointerstitial damage index (TII) as compared to SNX or control rats. In the SNX + GDP group the expression of carboxymethyllysine and methylglyoxal was significantly higher in the tubulointerstitium and the glomeruli compared to the SNX rats. Caspase 3 staining and TUNEL assay were more pronounced in the tubulointerstitium and the glomeruli of the SNX + GDP group. In SNX + GDP animals, the expression of the slit diaphragm protein nephrin, was significantly lower compared to SNX or control animals. CONCLUSION: In summary, our data suggests that GDP can significantly advance chronic kidney disease and argues that PD solutions containing high GDP might deteriorate residual renal function in PD.