Determinants of Outcome in Non-Septic Critically Ill Patients with Acute Kidney Injury on Continuous Venovenous Hemofiltration

Background/Aims: In view of ongoing controversy, we wished to study whether patient characteristics and/or continuous venovenous hemofiltration (CVVH) characteristics contribute to the outcome of non-septic critically ill patients with acute kidney injury (AKI). Methods: We retrospectively studied 102 consecutive patients in the intensive care unit (ICU) with non-septic AKI needing CVVH. Patient and CVVH characteristics were evaluated. Primary outcome was mortality up to day 28 after CVVH initiation. Results: Forty-four patients (43%) died during the 28-day period after the start of CVVH. In univariate analyses, non-survivors had more often a cardiovascular reason for ICU admission, greater disease acuity/severity and organ failure, lower initial creatinine levels, less use of heparin and more use of bicarbonate-based substitution fluid. The latter two can be attributed to high lactate levels and bleeding tendency in non-survivors necessitating withholding lactate-buffered fluid and heparin, respectively, according to our clinical protocol. In multivariate analyses, mortality was predicted by disease severity, use of bicarbonate-based fluids and lack of heparin, while initial creatinine and CVVH dose did not contribute. Conclusion: The outcome of non-septic AKI in need of CVVH is more likely to be determined by underlying or concurrent, acute and severe disease rather than by CVVH characteristics, including timing and dose

Влияние микроструктуры на электрохимическую активность, межфазный обмен и диффузию кислорода катодных материалов LSM—YSZ

Работа выполнена при финансовой поддержке УрФУ в рамках реализации Программы развития УрФУ для победителей конкурса «Молодые ученые УрФУ»

Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure

Contains fulltext : 152108.PDF (publisher's version ) (Open Access)Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD), yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL) expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-alphaklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal alphaklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5), calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b), whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a) and type 3 (PIT2) were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-alphaklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development

Partial nephrectomy and adenine-enriched dietary treatment induced CKD.

<p>Mice subjected to <b>(A)</b> partial nephrectomy (5/6Nx; n = 9) after 3 weeks and <b>(B)</b> adenine-enriched dietary treatment (ADE; n = 5) for either 2 or 4 weeks display elevated blood urea levels, when compared to sham-operated (n = 5) or control mice (n = 5), respectively. Renal expression of tubular injury marker NGAL is significantly elevated in <b>(C)</b> 5/6Nx mice and <b>(D)</b> ADE mice after 2 and 4 weeks, compared to sham-operated or control mice, respectively. Data are mean ± SEM. *: p<0.05 compared to either sham-operated or control mice.</p

The effects of induced CKD on general physiological parameters.

<p>Physiological measurements of mice subjected to 5/6Nx or sham operation, and subjected to ADE treatment for either 2 or 4 weeks or control diet. Data are collected after 24 hours housing in individual metabolic cages, and are indicated as mean ± SEM.</p><p>*: p<0.05 compared to either sham-operation or to control diet.</p><p>The effects of induced CKD on general physiological parameters.</p

CKD development altered renal expression of tubular phosphate transporters.

<p><b>(A)</b> mRNA expression of the renal NaP_i2a, PIT2 and NaP_i2b in mice with CKD development induced by either 5/6Nx (black bars) or <b>(B)</b> 2 weeks (black bars) and 4 weeks (gray bars) ADE treated mice ADE treatment, when compared to sham-operated (white bars) or control mice (white bars), respectively. Data are mean ± SEM. *: p<0.05 compared to either sham-operated or control mice.</p

Progression of CKD altered FGF23-αklotho signalling.

<p>Experimental CKD deregulates FGF23-αklotho signalling as reflected by <b>(A)</b> a tendency towards elevated circulatory FGF23 levels in 5/6Nx mice and <b>(B)</b> progressively elevated FGF23 levels in ADE treated mice compared to control mice. Renal mRNA expression of FGFR1 and αKlotho in <b>(C)</b> CKD induced 5/6Nx mice (black bars) compared with sham-operated groups (white bars) and in <b>(D)</b> 2 weeks (black bars) and 4 weeks (gray bars) ADE treated mice compared with control groups (white bars). <b>(E)</b> Representative immunoblot (all 3 groups are done in one blot) and <b>(F)</b> semi-quantitative analysis for αKlotho <b>(E</b>; upper panel) and β-actin <b>(E</b>; lower panel) protein expression in renal lysates of control or ADE treated mice, which indicates reduced renal αKlotho protein expression upon CKD. Data are mean ± SEM. *: p<0.05 compared to control mice.</p

Experimental kidney failure augmented renal vitamin-D synthesis and induced secondary hyperparathyroidism.

<p><b>(A)</b> PTH levels were elevated three weeks after 5/6Nx. <b>(B)</b> mRNA expression of Cyp27b1 and Cyp24a1 in 5/6Nx mice (black bars) compared with sham-operated group (white bars). <b>(C)</b> levels of 1,25-dihydroxy vitamin D₃ in the blood were measured in mice with 5/6Nx nephrectomy. <b>(D)</b> PTH levels were elevated progressively in ADE treated mice in both 2 weeks and 4 weeks ADE treated mice compared with control groups. <b>(E)</b> mRNA expression of Cyp27b1 and Cyp24a1 in CKD induced by 2 weeks (black bars) and 4 weeks (gray bars) ADE treated mice compared with control groups (white bars) and <b>(F)</b> levels of 1,25-dihydroxy vitamin D₃ increased in 2 weeks ADE treated mice in compare to control mice. This was significantly reduced in 4 weeks ADE treated mice in compare to 2 weeks ADE treated mice. Data are mean ± SEM. *: p<0.05 compared to either sham-operated or control mice.</p

FGF23 administration directly affected renal tubular calcium transport.

<p><b>(A)</b> Intravenous administration of recombinant FGF23 protein (dark-gray bars) results in increased TRPV5 and a tendency towards elevated calbindin-D_28k renal mRNA expression, when compared to vehicle-treated mice (white bars). Renal EGFP mRNA expression, as a surrogate marker for TRPV5 transcription tended to be increased following FGF23 administration compared to vehicle-treated mice. <b>(B)</b> Representative immunoblot and <b>(C)</b> semi-quantitative analysis of EGFP <b>(B</b>; upper panel) and β-actin <b>(B</b>; lower panel) protein expression in renal lysates of vehicle-treated or FGF23 injected mice. Blood <b>(D)</b> Ca²⁺ and <b>(E)</b> phosphate levels were measured following 24 hrs of FGF23 injection. <b>(F)</b> mRNA expression of the renal NaP_i2a and NaP_i2b in mice injected with FGF23 (gray bars), compared to vehicle-treated mice (white bars). Data are mean ± SEM. *: p<0.05 compared to control mice.</p

CKD development increased expression of tubular calcium transporters.

<p><b>(A)</b> mRNA expression of the renal apical Ca²⁺ transporter TRPV5 and intracellular calcium shuttling protein calbindin-D_28K in the CKD induced 5/6Nx mice (black bars) compared to sham-operated mice (white bars). <b>(B)</b> Representative microphotographs for renal TRPV5 and calbindin-D_28K protein expression in kidney tissue from CKD induced 5/6Nx mice and sham-operated mice. <b>(C)</b> mRNA expression of the renal apical Ca²⁺ transporter TRPV5 and intracellular calcium shuttling protein calbindin-D_28K in mice fed with ADE diet for 2 weeks (black bars) and 4 weeks (gray bars) compared with control diet fed mice (white bars). <b>(D)</b> Representative microphotographs for renal TRPV5 and calbindin-D_28K protein expression in kidney tissue from CKD induced ADE treated (4 weeks) and control mice. Bars represent 100 μm. Data are mean ± SEM. *: p<0.05 compared to either sham-operated or control mice.</p