The spectrum of glomerular and vascular kidney pathology associated with myeloproliferative neoplasms.

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.

Ultrasonographic assessment of the internal jugular vein for the estimation of central venous pressure in hemodialysis patients: A preliminary study.

PURPOSE: To investigate a new noninvasive method to assess central venous pressure (CVP) in hemodialysis patients, based on the ultrasonographic measurement of the collapsing point of the internal jugular vein (CVPni). MATERIALS AND METHODS: In this preliminary, noninterventional, single center study, we enrolled 22 dialyzed patients with an indwelling jugular catheter. CVPni was compared to the gold-standard invasive measurement of CVP using the central venous catheter (CVPi). Agreement between CVPi and CVPni was assessed by Bland and Altman Method. Correlation was assessed by linear regression. RESULTS: A strong correlation was observed between CVPi and CVPni (OR = 3.47 [2.96; 4.07], P < .0001). For overloaded patients, the area under the curve for the operating characteristic curve was 0.971 (IC95: 0.915; 1.000). For under-loaded patients, area under the curve was 0.971 (IC95: 0.917; 1.000). The mean bias between intra-individual CVPi and CVPni measures was 0.57 cm H2 O (SD: 3.1 cm H2 O). CONCLUSION: CVPni appears as a noninvasive and reliable technique. Further studies are required to confirm these results and to assess the direct clinical impact of this new method.

[Metformin associates lactic acidosis]. / Acidose lactique à la metformine.

Metformin Associates lactic acidosis (MALA) is a metabolic acidosis with higher anion gap, high levels of blood lactates and treatment by metformin. MALA is a very rare entity but is associated with high mortality (30 to 50%). The extrarenal blood purification may be necessary in emergency. Relatively good clinical tolerance contrasts with a very elevated serum lactate. There is always a trigger and hypovolemia is prevalent. MALA often occurs when its prescription is not indicated (renal failure, cardiac failure, hypovolemia, or patient aged over 80 years). Metformin must be stopped in situations of acute hypovolemia or frail patients as diuretics or blockers of the rennin-angiotensin-aldosterone system.

Improvement of renal hemodynamics during hypertension-induced chronic renal disease: role of EGF receptor antagonism.

The present study investigated mechanisms of regression of renal disease after severe proteinuria by focusing on the interaction among EGF receptors, renal hemodynamics, and structural lesions. The nitric oxide (NO) inhibitor N(G)-nitro-l-arginine-methyl ester (l-NAME) was administered chronically in Sprague-Dawley rats. When proteinuria exceeded 2 g/mmol creatinine, animals were divided into three groups for an experimental period of therapy of 2 wk; in one group, l-NAME was removed to allow reactivation of endogenous NO synthesis; in the two other groups, l-NAME removal was combined with EGF or angiotensin receptor type 1 (AT(1)) antagonism. l-NAME removal partially reduced mean arterial pressure and proteinuria and increased renal blood flow (RBF), but not microvascular hypertrophy. Progression of structural damage was stopped, but not reversed. The administration of an EGF receptor antagonist did not have an additional effect on lowering blood pressure or on renal inflammation but did normalize RBF and afferent arteriole hypertrophy; the administration of an AT(1) antagonist normalized all measured functional and structural parameters. Staining with a specific marker of endothelial integrity indicated loss of functional endothelial cells in the l-NAME removal group; in contrast, in the animals treated with an EGF or AT(1) receptor antagonist, functional endothelial cells reappeared at levels equal to control animals. In addition, afferent arterioles freshly isolated from the l-NAME removal group showed an exaggerated constrictor response to endothelin; this response was blunted in the vessels isolated from the EGF or AT(1) receptor antagonist groups. The EGF receptor is an important mediator of endothelial dysfunction and contributes to the decline of RBF in the chronic kidney disease induced by NO deficiency. The EGF receptor antagonist-induced improvement of RBF is important but not sufficient for a complete reversal of renal disease, because it has little effect on renal inflammation. To achieve full recovery, it is necessary to apply AT(1) receptor antagonism.