Recovery after dialysis

Mechanism-based inactivation results in formation of a covalent adduct between the active inhibitor and the enzyme, or between the active inhibitor and a substrate or cofactor molecule. If the mechanism involves covalent modification of the enzyme, then one should not be able to demonstrate a recovery of enzymatic activity after dialysis, gel filtration, ultrafiltration, or large dilution, as described in Chapters 5 to 7. Additionally, if the inactivation is covalent, denaturation of the enzyme should fail to release the inhibitory molecule into solution. If a radiolabeled version of the inactivator is available, one should be able to demonstrate irreversible association of radioactivity with the enzyme molecule even after denaturation and separation by gel filtration, and so on. In favorable cases one should likewise be able to demonstrate covalent association of the inhibitor with the enzyme by a combination of tryptic digestion and LC/MS methods. 

Fifty milliliters of the cell-free extract described above was fractionated by ammonium sulfate precipitation. The fraction precipitating between 30 and 50% saturation was redissolved in a total volume of 10 ml and dialyzed. The solution after dialysis occupied 12 ml and contained 30 mg protein/ml. Twenty microliters of the purified fraction catalyzed the phosphorylase reaction at a rate of 5.9 nmoles/min under the standard assay conditions. Calculate (a) the recovery of the enzyme and (b) the degree of purification obtained in the ammonium sulfate step. 

Five patients developed severe symptoms after receiving cefepime (31). The patients, three men and two women, aged 16-75 years, received 2 g/day (n — 3) A g/day n = 1) or 9 g/day n — 1). The symptoms started 12-16 days after the start of therapy. In all cases, the initial neurological symptoms (disorientation, confusion, and reduced consciousness) were progressive and were attributed to the infection. Facial or multifocal myoclonic movements occurred subsequently and were rapidly followed by convulsive or non-convulsive status epilepticus. The dose of cefipime had not been adjusted for renal function in any of the patients. Cefepime serum concentrations were measured in three cases, and were 72, 73, and 134 gg/ml. All the patients underwent hemodialysis, and the serum concentrations of cefepime fell to 4.3, 21, and 25 gg/ml respectively. In the other two patients, the serum concentrations after dialysis were 14 and 54 gg/ml, suggesting high concentrations before dialysis. There was complete recovery in four of the patients. One, a 73-year-old woman, died of multiorgan failure with refractory status epilepticus and coma. The authors referred to four... 

Unusual immune side-effects have also been reported in association with IFNa therapy. Chronic hemolytic uremic syndrome was observed in a patient with multiple myeloma treated with IFNa (De Broe ME, personal communication). The post bone marrow transplantation course was complicated and he received several nephrotoxic antibiotics. Three months later a treatment with IFNa was started. Towards the end of the treatment renal function deteriorated. There was partial renal recovery after cessation of therapy. Renal biopsy showed focal mesangio-capillary lesions, mesangiolysis and intracapillary thrombosis consistent with a chronic form of hemolytic uremic syndrome. Ra-vandi-Kashani et al. [49] and Harvey et al. [50] reported 3 other cases of HUS/TTP. Two patients developed renal failure requiring dialysis. E. coli OH157.H7 was grown from the stool of one patient. 

Table 3 Recovery rates of the sodium cations with different analytical methods before and after dialysis purification...

IL-18 is a member of the IL-1 family of cytokines. It is present as an inactive precursor in most cell types and is activated by cas-pase-1 activity [71]. IL-18 binds to IL-18 receptors initiating a signal transduction cascade ultimately activating NFkB, which is responsible for its pro-inflammatory effects [71]. IL-18 has been shown to be elevated in urine of patients with acute tubular necrosis [72] and has also been shown to predict mortality in intensive care patients [73]. In addition, urinary IL-18 has been shown to predict dialysis and graft recovery after kidney transplantation [74] and contrast-induced nephropathy [75]. IL-18 is also expressed in cells in vitro, and IL-18 expression has been shown to be induced by TGF-beta in cultured human proximal tubule cells [76],... 

Hall IE, Yarlagadda SG, Coca SG, Wang Z, Doshi M, Devarajan P, Han WK, Marcus RJ, Parikh CR (2010) IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 21(1) 189-197. doi 10.1681/ASN.2009030264... 

Information in support of this hypothesis has been obtained in detailed studies on the inactivation kinetics and mechanism of pig and beef liver MAO-A by A -cyclopropyl-A-arylalkylamines. The structures and some kinetic properties of this second group of MAO inhibitors are summarized in Table III. The inactivation characteristics of the A/-cyclopropylamines are generally similar to those of the propargylamines (1) time-dependent, first-order loss of enzyme activity, saturation kinetics, and protection from inactivation by substrate or product (2) pH-dependent rate of inactivation corresponding to the pH dependence of enzyme activity (3) little activity recovery after exhaustive dialysis (4) partitioning between normal product formation and inactivation and (5) time-dependent conversion of the covalently bound FAD cofactor from the oxidized to a reduced form, which is fairly resistant to reoxidation. An important differ-... 

Contrast nephrotoxicity presents most commonly as nonoliguric, transient tubular enzymuria. However, irreversible oliguric (urine volume < 500 mL/day) kidney injury requiring dialysis has been reported in high risk patients including diabetics with pre-existing kidney disease. Kidney injury typically manifests within the first 12-24 h after the contrast study. The serum creatinine concentration usually peaks between 2 and 5 days after exposure, with recovery after 4—10 days. Urinalysis typically reveals only hyaline and granular casts, but may also be completely bland (Murphy et al. 2000). The urine sodium concentration and fractional excretion of sodium are frequently low. 

Depending on the purity aind the history of the dry enzyme preparation, recovery yields of 90-100% expressed activity of the immobilized enzyme have been achieved. The activity of the soluble enzyme preparation after dialysis is approximately 400 IGIU/ ml and a 2X quantity of enzyme is utilized for immobilization with roughly 50% of the offered soluble enzyme being recovered after immobilization and 45-50% of the offered soluble enzyme resulting in expressed activity on the reactor when operated under the aibove conditions. Depending upon the activity of the purified enzyme, the activity of the carrier after immobilization is typically 600 IGIU/g. 

At plasma nickel concentrations of about 3 mg/L, patients had adverse effects including headaches, nausea, vomiting, and weakness recovery occurred 3 to 13 h after cessation of dialysis... 

Melling and Atkinson29 investigated nuclease treatment as a method for the removal of nucleic acids from bacterial suspensions. Two strains of E. coli were used and for both the strains the nuclease treatment was effective in depolymerizing nucleic acids and, hence, in recovery of supernatant after centrifugation to remove cell debris from disrupted cells. The nucleotide content in the supernatant was found to be 15-20% of total proteins and nucleic acids. The nucleotide content in the supernatant was reduced to a very low level by ammonium sulfate precipitation followed by dialysis of the redissolved precipitate. As stated earlier, direct precipitation of nucleotides resulted in significant residual nucleotides in the proteins. 

The process of diffusion dialysis is also mentioned briefly, as an attempt to recover spent acid from WTR, after alum recovery. The objective of this process is to estimate the efficacy of the process in (a) raising the pH of the treated WTR and (b) lowering the pH of the fresh WTR before undergoing alum recovery in the DMP. 

Renal insufficiency after high dosages of intravenous immunoglobulin has been observed, mostly in patients with pre-existing renal disease (81). Acute renal insufficiency occurred within 7 days after the administration of intravenous immunoglobulin, with a peak at 5 days. About 40% of patients needed dialysis and 15% died despite treatment (all with severe underlying diseases) the mean time to recovery in survivors was about 10 days (82). 

When serum methotrexate concentrations are high, leu-covorin (folinic acid) rescue may protect against renal damage. Methotrexate concentrations are only transiently lowered by hemoperfusion, and they are unaffected by peritoneal dialysis once there is acute renal insufficiency. Sustained reductions in drug concentrations and recovery of renal function have been reported after charcoal hemoperfusion followed by hemodialysis (63,64). 

Acute kidney injury can be severe with foscarnet. Some degree of kidney injury has been reported to occur in as many as two-thirds of patients treated with foscarnet and has been a dose-limiting toxicity in 10-20% of cases [51-56]. Despite dose reduction or discontinuation of foscarnet, azotemia typically progresses for at least a few days before resolving. It may be possible to continue foscarnet at reduced doses in some patients with mild azotemia. Foscarnet-induced AKI is usually reversible, although temporary dialysis may be required [57]. Recovery may be slow, particularly in patients with preexisting kidney insufficiency. Elevated serum creatinine concentrations may persist for several months after discontinuation of foscarnet. Foscarnet nephrotoxicity may be also associated with mild proteinuria. Volume expansion with isotonic saline was effective in reducing the incidence of foscarnet nephrotoxicity to 13%, compared to 66% in non-hydrated historical controls, and allowed patients with prior kidney insufficiency to receive foscarnet without further reduction of kidney function [54, 58]. Intermittent, rather than continuous, infusion of foscarnet may also reduce the incidence of nephrotoxicity [52]. 

In their series of 32 patients Neto et al [13] showed that seven patients died after intoxication episodes. The main characteristics of the patients who died were convulsive activities in 6 and severe mental confusion in all 7 patients, while 2 of them presented hemodynamic instability (hypotension and shock). Most of the patients who died were treated by peritoneal dialysis or did not receive any other kind of treatment. The other 25 patients improved without sequelae and they were treated either by conventional hemodialysis, daily hemodialysis (6 to 8 hours duration) or even by continuous methods of dialysis. A few patients were treated by peritoneal dialysis. Complete recovery time in these 25 patients ranged from 1 to 12 days (mean 4.4 days and median 4.0 days). 

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