Fluoro-Photoacoustic Polymeric Renal Reporter for Real-Time Dual Imaging of Acute Kidney Injury

Photoacoustic (PA) imaging agents detect disease tissues and biomarkers with increased penetration depth and enhanced spatial resolution relative to traditional optical imaging, and thus hold great promise for clinical applications. However, existing PA imaging agents often encounter the issues of slow body excretion and low-signal specificity, which compromise their capability for in vivo detection. Herein, a fluoro-photoacoustic polymeric renal reporter (FPRR) is synthesized for real-time imaging of drug-induced acute kidney injury (AKI). FPRR simultaneously turns on both near-infrared fluorescence (NIRF) and PA signals in response to an AKI biomarker (γ-glutamyl transferase) with high sensitivity and specificity. In association with its high renal clearance efficiency (78% at 24 h post-injection), FPRR can detect cisplatin-induced AKI at 24 h post-drug treatment through both real-time imaging and optical urinalysis, which is 48 h earlier than serum biomarker elevation and histological changes. More importantly, the deep-tissue penetration capability of PA imaging results in a signal-to-background ratio that is 2.3-fold higher than NIRF imaging. Thus, the study not only demonstrates the first activatable PA probe for real-time sensitive imaging of kidney function at molecular level, but also highlights the polymeric probe structure with high renal clearance.     

Acute kidney injury secondary to chlorine dioxide use for COVID-19 prevention

Chlorine dioxide has been historically used as a disinfecting agent for drinking water supplies and surfaces. Widespread use as an alternative option for prevention and treatment of COVID-19 has emerged due to a lack of specific treatment. We present the case of a 55-year-old male who developed acute kidney injury and disseminated intravascular coagulation after chlorine dioxide prophylactic ingestion, with regression after therapy with hemodialysis.     

Can dialyzer membrane selection affect outcomes in patients with acute kidney injury requiring dialysis?

The choice of dialyzer membrane may potentially affect not only solute clearances but also blood-dialyzer interactions. Although on one hand alteration of the dialyzer surface or pore size to increase inflammatory mediator loss may potentially be beneficial for patients with acute kidney injury (AKI), dialyzer membrane interactions, which precipitate intradialytic hypotension, may worsen AKI. Several years ago cellulosic membrane dialyzers were shown to reduce both patient survival and renal recovery in patients with AKI. This review looks at the earlier studies of dialyzer membrane choice and outcomes in AKI, besides discussing the newer developments in membrane technology for patients with AKI.     

Comparison of risk factors for contrast‐induced acute kidney injury between patients with and without diabetes

Although it is well known that diabetics are at a higher risk of contrast‐induced acute kidney injury (CI‐AKI) than nondiabetic patients, the reason for this discrepancy is not well known. Thus, in this study, we compared the predisposing factors for CI‐AKI between patients with and without diabetes. We prospectively studied 290 consecutive in‐hospital patients including 88 diabetics undergoing coronary angiography or a percutaneous coronary intervention in Kowsar hospital, and we compared risk factors for CI‐AKI between diabetic and nondiabetic patients. CI‐AKI was defined as RIFLE criteria within 48 hours after contrast exposure. The incidence of CR‐AKI was significantly higher in diabetic patients compared with nondiabetics (P<0.05). The incidence of CI‐AKI was significantly higher in patients with diabetes and left‐ventricular ejection fraction ≤40%, hypercholesterolemia, serum creatinine ≥1.1 mg/dL, estimated glomerular filtration rate (eGFR) <90 mL/min, Contrast volume ≥80 (mL), maximum safe contrast volume factor of 1.5, and dehydration, while in nondiabetics, a significantly higher incidence of CR‐AKI was observed in those with serum creatinine ≥1.1 mg/dL (P=0.02) and/or eGFR<60 mL/min (P=0.01). Multiple logistic regression analysis showed hyperchlosteremia to be the strongest predictor of AKI (P=0.01, B:14.5) in diabetics, followed by eGFR<90 (P=0.05, B:12.4) but, in nondiabetics, only eGFR<60 predicted the occurrence of CI‐AKI (P=0.04, B:2.3). It seems that the predisposing factors to CI‐AKI differ in diabetics and nondiabetics. In patients with diabetes, hypercholesterolemia is the strongest predictor of CI‐AKI, followed by eGFR and diabetics are at risk for CI‐AKI in the early stage of chronic kidney disease (stage 2), accounting for the higher incidence of CI‐AKI in them.     

Thrombosed hemodialysis access as an unusual source of emboli in the upper extremity of a kidney transplant recipient

Arteriovenous fistula (AVF) is no longer used in kidney transplant recipients. However, there is no consensus regarding whether or not to ligate a well‐functioning AVF after successful kidney transplantation, particularly in patients with well and stably functioning kidney transplants. Most AVFs without complications are left in situ and more than one‐third of native AVFs close spontaneously. The currently accepted policy toward thrombosed AVFs is retention within the patient's extremity without treatment. These thrombosed AVFs seldom cause serious problems. However, when combined with aneurysmal dilatation of the proximal vein adjacent to the arterial anastomotic area, the AVF could act as the source of distal arterial emboli. This is very similar clinical scenario to that observed in embolization from a peripheral arterial aneurysm. Here we describe a case report of upper extremity ischemia following massage of a thrombosed aneurysmal AVF. The patient was successfully treated with a combination of catheter‐directed thromboaspiration, thrombolysis, and surgical repair of the thrombosed AVF. To the best of our knowledge, this is the first report of upper extremity embolism after massage of a thrombosed aneurysmal AVF involving this combined treatment.     

Renal involvement in mushroom poisoning: The case of Orellanus syndrome

Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little‐known intoxication.     

Management of acute kidney injury in neurotrauma

Fortunately, the incidence of acute kidney injury (AKI) in neurotrauma is low and decreasing. Whereas the majority of AKI occurs in older patients with pre-existing chronic kidney disease, neurotrauma typically occurs in children and young adults with normal renal function. The development of outreach trauma teams has improved initial resuscitation, reducing both volume responsive and volume unresponsive cases of AKI. Most cases occur in the setting of multiple organ trauma with muscle injury, or patients who subsequently develop multiple organ failure. Once AKI has developed and renal replacement therapy is required, continuous modalities of renal replacement therapy offer an advantage to the patient with compromised cerebral perfusion and intracranial hypertension, by reducing the rate of change in serum urea, compared with standard intermittent therapies of hemodialysis and hemofiltration, thus minimizing abrupt changes in serum osmolality. Continuous hemodialysis and hemofiltration are better suited to maintain a normal or high serum sodium and thermal losses through the extracorporeal circuit, than peritoneal dialysis. Dialyzers should preferably be minimally bioincompatible and of a small surface area. In patients at risk of intracranial hemorrhage and those with invasive intracranial monitoring, systemic anticoagulants should either be avoided or regional anticoagulants should be used.     

Lipoprotein (a) in Chronic Renal Failure: Effect of Maintenance Hemodialysis

Background:  Coronary artery disease accounts for significant morbidity and mortality in patients with chronic kidney disease (CKD). Besides the higher prevalence of traditional risk factors, several uremia-related factors may play a role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a) (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well understood. The present work was carried out to study the Lp(a) levels in Stage 4 and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients with Stage 5 CKD.
Methods:  The study subjects included 15 patients with Stage 4 CKD, 15 patients with Stage 5 CKD, and 15 age- and sex-matched healthy controls. Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD were dialyzed two to three times weekly for 4 hr during each session.
Results:  Mean Lp(a) levels were significantly higher in patients with CKD than in control patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 ± 19.5 mg/dL, whereas in Stage 5 CKD the level was 49.0 ± 30.9 and in healthy controls it was 22.2 ± 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant fall in Lp(a) levels by 23.6% (P < 0.001).
Conclusions:  The results of this study show that increases in Lp(a) levels start early during the course of CKD and become more pronounced with increased severity of disease. Initiation of MHD lowers Lp(a) levels and may have a long-term beneficial effect on cardiovascular morbidity and mortality.     

Digitizing floating marine platform coordinate measurements for a knowna priori probability of occurrence in a permissible drilling region

An algorithm is described for digitizing the coordinate measurements on floating marine platforms subject to a known a prioriprobability of the platform being in a permissible drilling region, which enables one to determine the digitization interval from the rate of displacement and the statistical characteristics of the measured coordinates.Translated from Izmeritel'naya Tekhnika, No. 7, pp. 14–16, July, 1994.     

Hemodialysis Systems for Intermittent,Semi-Continuous,and Continuous Therapies in Acute Renal Failure

As is the case in end-stage renal disease (ESRD), both intermittent and continuous renal replacement therapies (RRTs) are employed in acute renal failure (ARF). In fact, a continuum of treatment options is available in ARF. At one end of the ARF RRT spectrum is conventional intermittent hemodialysis (IHD), in which relatively high blood and dialysate flow rates are used (typically ≥250 and 500 mL/min, respectively). Continuous renal replacement therapies (CRRTs), which employ much lower flow rates, comprise the other end of the spectrum. Finally, hybrid therapies, which combine characteristics of both IHD and CRRT, have recently been described. These therapies’ removal mechanisms for solutes over a broad molecular weight range are discussed. An understanding of these mechanisms is important when determining the amount of therapy that can be provided by any RRTs. Additional studies are required to improve the understanding of solute removal by the various RRT used in ARF.     

Present status and future perspectives on the development of bioartificial kidneys for the treatment of acute and chronic renal failure patients

A bioartificial renal tubule device (BTD) consisting of a hollow-fiber module and human proximal tubular epithelial cells has been completed technically by Humes and colleagues and a few other groups. Humes and colleagues developed BTD, treated acute kidney injury patients with multiorgan failure by continuous hemofiltration (CHF) in conjunction with BTD, and reported a significantly higher survival rate than that by CHF with BTD without cells in the Food and Drug Administration phase IIa trial. However, BTD has never been approved by the US Government, as the CHF+BTD treatment did not show a significant difference from the control group in the phase IIb trial. Human proximal tubular epithelial cells were confirmed to be overgrown on artificial membrane, which resulted in the inhibition of active transports and the metabolism of essential substances. Function of the BTD could be maintained in a U0126-contained medium, even if the BTD had to have been waited by a new acute kidney injury patient for several weeks. For wearable kidneys, heparin-covalently bound membrane or methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated membranes are candidates for antithrombogenic hemofilters, while endothelial progenitor cells from a cord blood, CD133(+) cells-attached hemofilter in which the permeability of the cells was enhanced by the enlarged diameter of fenestrae by treating with cytochalasin B are another candidate. The MPC blend membrane containing 1% of the MPC polymer in polysulfone was developed as a BTD module. MPC was 7 times larger at the sponge layer than at the skin layer of the membrane, resulting in hemocompatibility at the sponge layer and cytocompatibility at the skin layer.     

Outcomes of patients with end‐stage renal disease (ESRD) under chronic hemodialysis requiring continuous renal replacement therapy (CRRT) and patients without ESRD in acute kidney injury requiring CRRT: A single‐center study

In most continuous renal replacement therapy (CRRT) studies, end‐stage renal disease (ESRD) patients were excluded and the outcomes of patients with ESRD treated with chronic hemodialysis (HD) were unknown. The purposes of this study were to (1) evaluate short‐term patient survival and (2) compare the survival of conventional HD patients needing CRRT with the survival of non‐ ESRD patients in acute kidney injury (AKI) requiring CRRT. We evaluated adults (>18 years) requiring CRRT who were treated in the intensive care unit (ICU) at Kosin University Gospel Hospital from January 1, 2009 to December 31, 2010. A total of 100 (24 ESRD, 76 non‐ESRD) patients underwent CRRT during the study period. Patients were divided into two major groups: patients with ESRD requiring chronic dialysis and patients without ESRD (non‐ESRD) with AKI. We compared the survival of conventional HD patients requiring CRRT with the survival of non‐ ESRD patients in AKI requiring CRRT. For non‐ESRD patients, the 90‐day survival rate was 41.6%. For ESRD patients, the 90‐day survival rate was 55.3%. Multivariate Cox proportional hazards analyses demonstrated that conventional HD was not a significant predictor of mortality (hazard ratio [HR]: 0.334, 95% confidence interval [CI]: 0.063–1.763, P = 0.196), after adjustment for age, gender, presence of sepsis, APACHE score, use of vasoactive drugs, number of organ failures, ultrafiltration rate, and arterial pH. The survival rates of non‐ESRD and ESRD patients requiring CRRT did not differ; ESRD with conventional HD patients may be not a significant predictor of mortality.     

The possibility of renal function recovery in chronic hemodialysis patients should not be overlooked: Single center experience

Chronic hemodialysis is implemented when irreversible loss of kidney function occurs. Sometimes renal recovery is overlooked. From January 2005 to December 2014, we identified 28 patients hemodialyzed for more than 3 months who had renal replacement therapy discontinued. The group consisted of 17 (57.7%) males and 11 (42.3%) females. Patients were 18–87 years old. Time of hemodialysis ranged from 3 to 97 months. Of note, 14 (50%) patients were referred from local dialysis units for solution of vascular access problems. In 13 (46.2%) patients dialysis was abandoned within the first 6 months, in 5 (17.8%) patients between 6 and 12 months, and in 10 (35.7%) patients beyond 12 months. Estimated dialysis‐free survival was 94.4% (SE 0.054) and 82% (SE 0.095) at 12 and 24 months, respectively. All physicians must be aware of possible kidney function improvement. In patients with preserved diuresis fall in periodical urea or creatinine measurements might be a sign of renal recovery.     

Acute kidney injury in a postpartum woman with paroxysmal nocturnal hemoglobinuria: A case report and literature review

Paroxysmal nocturnal hemoglobinuria is a rare clonal hematopoietic stem cell disorder characterized by intravascular hemolysis, hemoglobinuria, and inflammatory thrombotic state. Intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) can lead to acute and chronic renal injury through hemoglobin‐mediated toxicity. A 32‐year‐old pregnant woman with myelodysplastic syndrome was admitted to our hospital with severe preeclampsia. Shortly after an urgent caesarean section, she became obtunded and showed signs of acute kidney injury (AKI) with anuria, severe intravascular hemolysis, and hypermagnesemia. She was diagnosed with PNH with a positive Ham test and flow cytometry analysis. Renal magnetic resonance imaging revealed decreased signal intensity in the renal cortex due to hemosiderin deposition. Hemodialysis, plasma exchange, and administration of corticosteroids ameliorated her clinical condition and renal function. This case illustrates that careful management is required to prevent postpartum AKI in pregnant women with PNH.     

Measurement of Hemodialysis Adequacy in a Changing World

Defining adequacy of dialysis remains an elusive goal. The application of the Kt/V_urea concept to clinical dialysis was a major improvement in trying to define a dialysis dose. Intuitively, the Kt/V concept makes a great deal of sense: the urea clearance of the dialyzer during dialysis (K), multiplied by the time (t) of dialysis, divided by the patient's urea distribution volume (V) ought to give the best number to compare the efficiency of dialyses that patients receive. There are, however, many pitfalls associated with the whole Kt/V_urea concept.     

Selecting a paraxial region profile for the accelerating structure of an electron-positron collider

The effect of perturbations in the profile of a paraxial region boundary on the electrodynamic characteristics of the accelerating structure of an electron-positron collider has been studied. In addition to the traditional elliptic profiles, configurations that form an electric field with a homogeneous radial component synchronous with injected electrons have been considered. It is established that, for a surface of the latter type, the electromagnetic field structure is more stable with respect to profile perturbations.     

Dialysis disequilibrium syndrome and other treatment complications of extreme uremia: a rare occurrence yet not vanished

Severe uremia is now a rare occurrence in most developed nations, and yet is still present in many countries of the world. It includes clinical manifestations such as calciphylaxis and uremic frost, which are now rarely seen. Patients with extremely high levels of blood urea nitrogen (above 175 mg/dL) are at a higher risk of experiencing first-time hemodialysis-related complications, in particular dialysis disequilibrium syndrome (DDS). DDS is a central nervous disorder characterized by a wide variety of neurological symptoms that range from nausea and vomiting to even death due to cerebral edema. There are 2 main theories to explain its pathophysiology: the reverse urea effect, which considers that the shift of urea between brain intracellular space and plasma is not immediate, causing a higher concentration of urea within the brain and leading to cerebral edema. The second theory considers that after hemodialysis, patients have transient paradoxical metabolic acidosis within the central nervous system, displacing Na(+) and K(+) from organic anions, making them osmotically active and again leading to cerebral edema. The main goal is to prevent the occurrence of DDS, for which there are several proposed measures including continuous renal replacement therapies. Once established, treatment should be focused on supportive therapy. Another uncommon phenomenon described in patients who initiate hemodialysis is transient pulmonary leukocyte margination, which in conjunction with an inflammatory milieu, may lead to non-cardiogenic pulmonary edema. We present the case of a young adult with severe uremia who, despite application of recommended measures, developed DDS and non-cardiogenic pulmonary edema.