Ischemic acute renal failure: an inflammatory disease?

Inflammation plays a major role in the pathophysiology of acute renal failure resulting from ischemia. In this review, we discuss the contribution of endothelial and epithelial cells and leukocytes to this inflammatory response. The roles of cytokines/chemokines in the injury and recovery phase are reviewed. The ability of the mouse kidney to be protected by prior exposure to ischemia or urinary tract obstruction is discussed as a potential model to emulate as we search for pharmacologic agents that will serve to protect the kidney against injury. Understanding the inflammatory response prevalent in ischemic kidney injury will facilitate identification of molecular targets for therapeutic intervention.     

Should we use diuretics in acute renal failure?

Because oliguria is a bad prognostic sign in patients with acute renal failure (ARF), diuretics are often used to increase urine output in patients with or at risk of ARF. From a pathophysiological point of view there are several reasons to expect that loop diuretics also could have a beneficial effect on renal function. However, clinical trials on the prophylactic use of loop diuretics rather point to a deleterious effect on parameters of kidney function. In patients with established ARF loop diuretics have been shown to increase urine output, which may facilitate patient management. A beneficial effect on renal function has, however, not been demonstrated. On the other hand, such an effect cannot be excluded because the available trials lack statistical power. Possible explanations for the absence of a renoprotective effect are discussed. The evidence for a renoprotective effect of mannitol is restricted to the setting of renal transplantation.     

Açai berry extract attenuates glycerol-induced acute renal failure in rats

Abstract

Acute renal failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Açai berry extract (ABE) on glycerol-induced ARF in rats. Results of the present study showed that rat groups that received oral ABE in a dose of 100 and 200?mg/kg/day for 7 days before or 7 days after induction of ARF by a single intramuscular glycerol injection reported a significant improvement in kidney functions tests [decrease in serum urea, serum creatinine, and blood urea nitrogen (BUN)] when compared to the ARF model groups. Moreover, there was significant amelioration in renal oxidative stress markers [renal catalase (CAT), renal reduced glutathione (GSH)] and renal histopathological changes in the ABE-treated groups when compared to ARF model groups. The most significant improvement was reported in the groups where ABE was administered in a dose 200?mg/kg/day. These results indicate that ABE has a potential role in ameliorating renal damage involved in ARF.     

Differences between ‘intact’ PTH and 1–84 PTH assays in chronic renal failure and dialysis

Intact parathyroid hormone (iPTH) assays overestimate actual PTH as they cross-react with non (1–84) PTH fragments (C-PTH) that accumulate in renal failure. New assays that measure just 1–84 PTH (CAP-PTH) are now available. It has been suggested that there is a linear relationship between the two assays; however, increased C-PTH levels are found as glomerular filtration rate (GFR) declines and in patients on dialysis. We investigated the relationship between iPTH and CAP-PTH in children with chronic renal failure (CRF) managed conservatively and on dialysis. We investigated 241 children, 156 with a GFR <60 ml/min per 1.73 m² managed conservatively, 49 post renal transplant (and GFR <60 ml/min per 1.73 m²) and 36 on dialysis, by measuring PTH levels by iPTH and CAP-PTH assays. Multiple regression analysis comparing differences between PTH levels in each patient group was performed. Correlation slopes between iPTH and CAP-PTH assays differed between CRF and dialysis patients (P=0.001). These assays perform differently in CRF and dialysis patient groups. Studies investigating the correlation between newer assays and bone histology are required to determine whether these more-specific PTH assays are superior surrogate markers of bone turnover.     

Chronic renal failure in children: an epidemiological survey in Lorraine (France) 1975–1990

A comprehensive investigation in Lorraine from 1975 to 1990 identified 127 children (73 boys, 54 girls) under 16 years with chronic renal failure (CRF). From 1975–1980 to 1985–1990 the mean annual incidence of pre-terminal CRF decreased from 12.7 to 7.5 per million children under 16 years of age. The incidence of end-stage renal disease (ESRD) in children increased from 5.6 to 7.5 per million with a peak of 9.1. The prevalence of preterminal CRF was variable (29.4–54) and the prevalence of ESRD increased from 15.5 to 37.0 per million children. Acquired nephropathies were observed in 30.7% and congenital nephropathies in 68.5%. Although patients with acquired nephropathies had only slightly higher serum creatinine levels, they progressed more rapidly to ESRD than those with congenital disease: mean 1.8 years versus 3.85 years after diagnosis of pre-terminal of CRF (P<0.02). Ten years after onset of pre-terminal CRF, 94% with acquired and 69% of those with congenital nephropathies had started renal replacement therapy (P<0.001). It is unclear whether the decrease in preterminal CRF reflects a reduced number of children with kidney disease reaching CRF or is the result of a real delay in the progression due to better therapeutic management.     

Nutrition and chronic renal failure in rats: what is an optimal dietary protein?

In chronic uremia (CRF), malnutrition is an important determinant of morbidity in adults and impaired growth in children. Causes of malnutrition include anorexia and abnormal protein and amino acid metabolism. To determine how different levels of dietary protein and CRF interact to influence growth and nutritional status, CRF and sham-operated, pair-fed control rats were fed isocaloric diets containing 8, 17, or 30% protein for 21 d to mimic dietary regimens recommended for CRF patients: the minimum daily requirement; the recommended daily allowance; or an excess of dietary protein. Serum creatinine did not differ between groups of CRF rats but blood urea nitrogen was lowest in CRF rats fed 8% protein (P < 0.001). CRF rats eating 30% protein gained less weight and length compared to their controls or CRF rats fed 8 or 17% protein (P < 0.05); they also had acidemia. CRF rats fed 8% protein had the highest efficiency of utilization of protein for growth, while 17% protein promoted the highest efficiency of utilization of food and calories for growth. Notably, CRF rats eating 30% protein had the lowest protein efficiency; their calorie intake was also the lowest because of anorexia. Plasma branched-chain amino acids were progressively higher in control rats eating 8, 17, or 30% protein. CRF rats fed 8 or 17% protein had lower branched-chain amino acid concentrations compared with CRF rats fed 30% protein. In CRF, it is concluded that excessive dietary protein impairs growth but a low-protein diet does not impair nutritional responses and permits utilization of protein for growth if calories are sufficient.     

Is peritoneal dialysis adequate for hypercatabolic acute renal failure in developing countries?

BACKGROUND: Peritoneal dialysis (PD) is a therapeutic option for acute renal failure (ARF) in developing countries, despite concerns about inadequacy. Shorter and more efficient tidal peritoneal dialysis (TPD) was compared with continuous equilibrating peritoneal dialysis (CEPD) therapy in ARF by using their adequacies as accepted standards and analyzing the solute reduction indices (SRI). METHODS: A prospective, randomized crossover trial was performed in patients with mild to moderate hypercatabolic ARF who were assigned to CEPD and TPD therapy after an adequate washout period. Solute clearances (Kt/V, normalized creatinine clearances) were compared to NKF guidelines. Potassium and phosphate clearances, dextrose absorption, protein losses and costs were compared. Kt/V was compared to SRIdialysate, SRIKt/V. RESULTS: Eighty-seven patients with ARF received 236 sessions of dialysis (118 in each treatment). TPD resulted in higher clearances of solutes than CEPD (creatinine and urea clearances in mL/min of 9.94 +/- 2.93, 6.74 +/- 1.63 and 19.85 +/- 1.95, 10.63+/- 2.62, respectively, P=0.001). TPD and CEPD normalized creatinine clearances (L/week/1.73 m2 BSA) and Kt/V values were 68.5 +/- 4.43, 58.85 +/- 2.57 and 2.43 +/- 0.87, 1.80 +/- 0.32, respectively. CEPD did not meet standards of adequacy. TPD resulted in greater potassium and phosphate clearances, less dextrose absorption and was less expensive. CEPD resulted in less protein loss. Kt/V corresponded to SRIdialysate 0.88 +/- 0.12 (P=0.076). CONCLUSION: TPD produced higher solute clearances in less time with greater protein loss. CEPD just fell short to meet the dialysis adequacy standard. However, both TPD and CEPD are reasonable options for mild-moderate hypercatabolic ARF. Kt/V appropriately estimates solute removal in PD.     

Is continuous veno-venous hemofiltration for acetaminophen-induced acute liver and renal failure worthwhile?

We describe a patient with acute liver and renal failure secondary to acetaminophen and chronic alcohol abuse who was treated aggressively with oral acetylcysteine, continuous renal replacement therapy, glucose and branched-chain amino acid intravenous feeding and ventilatory support. The patient had a predicted mortality of > 95% without liver transplantation however, with intensive ventilatory, renal, and nutritional support he made a complete recovery. We discuss the benefits of aggressive supportive therapy and suggest that continuous renal replacement therapy may allow gentle fluid removal, excellent control of cerebral edema and intravenous feeding that may favorably influence prognosis.     

McKittrick–Wheelock syndrome: a rare cause of acute renal failure and hypokalemia not to be overlooked

McKittrick–Wheelock syndrome is a rare disorder in which a colorectal tumor (usually a villous adenoma) determines secretory mucous diarrhea, which in turn leads to prerenal acute renal failure, hyponatremia, hypokalemia and metabolic acidosis. Even though the outcome is usually favorable with complete recovery after surgery, the diagnosis is often delayed, making the patient susceptible to life-threatening complications, mainly severe acidosis and hypokalemia. We present two paradigmatic cases with extreme electrolytes imbalance and complete recovery following the appropriate treatment. The pathogenesis of this degenerative condition is discussed in detail.     

Tacrolimus in acute renal failure: does L‐arginine‐infusion prevent changes in renal hemodynamics?

Nephrotoxicity is one of the main side effects of calcineurin-inhibitors. The influence of tacrolimus on the renal vasculature has not been well described. We have therefore examined the effects of tacrolimus on renal functional parameters as well as the contribution of the NO-system in a model of ischemic acute renal failure (ARF). Induction of ARF was achieved by clamping both renal arteries of female Sprague-Dawley rats. During the experiment, RBF, GFR, MAP, RVR and FENa were determined during infusion of vehicle, TAC, TAC and the NOS-activator L-arginine, and TAC and NOS-inhibition due to L-NMMA. TAC induced a significant rise in RVR with further decrease of RBF and GFR. Simultaneous L-arginine-infusion could reverse these effects during the infusion without complete restoration to preischemic levels. NOS-inhibition increased MAP and RBF without any effect on GFR. FENa did not differ significantly between the groups. Tacrolimus in the situation of ischemic acute renal failure causes vasoconstriction of pre- and postglomerular vessels with a further deterioration of renal function. L-arginine abolishes the functional deterioration, most likely due to increased NO-liberation. Received: 4 October 1999 Revised: 16 March 2000 Accepted: 18 September 2000     

A case with acute renal failure complicated by Waldenström's macroglobulinemia and cryoglobulinemia

We encountered a 53-year-old man associated with acute renal failure caused by Waldenstr?m's macroglobulinemia and type I cryoglobulinemia. Treatment with prednisolone and cyclophosphamide induced a rapid recovery from acute renal failure. Renal histology revealed endocapillary proliferation and lobular formation with scattered subendothelial, amorphous and periodic acid-Schiff (PAS)-positive materials in the glomerular capillaries which were positive for IgM on immunofluorescence study. Although the exact mechanism for pathophysiology of acute renal failure remains unknown, treatment with prednisolone and cyclophosphamide could induce a rapid recovery from acute renal failure accompanied by Waldenstr?m's macroglobulinemia and type I cryoglobulinemia.     

The diagnosis of acute renal failure in intensive care: mongrel or pedigree?

Acute renal failure is common in the intensive care unit; it is well recognised that patients who develop acute renal failure have a high mortality rate. While there have been improvements in the management of acute renal failure, the mortality remains high. Acute renal failure is easily diagnosed biochemically and clinically but it is not a single disease entity. It is a syndrome that affects a very heterogeneous population. Studies of acute renal failure and of the impact of renal replacement therapy in intensive care are usually inconclusive, which may be the natural consequence of studying a syndrome. This article focuses on the more uncertain features of acute renal failure, the problems of investigating acute renal failure as a disease and the difficulties of applying the results of a study of a heterogeneous population to the management of individuals.     

Any heart failure treatments associated with worsening renal function in patients admitted due to acute heart failure?

BackgroundWorsening renal function (WRF) occurs in approximately 25% of acute heart failure patients, and both baseline characteristics and heart failure treatment may increase the risk of WRF. This study aimed to evaluate additional risk factors for WRF in acute heart failure, particularly those related to heart failure treatment.MethodsThis was a retrospective, observational, analytical study. The inclusion criteria were age 18 years or over, hospital admission due to acute heart failure, and having undergone at least two serum creatinine tests during admission. The eligible patients were classified into two groups: WRF and non-WRF. Predictors for WRF (including treatment parameters) were determined using logistic regression analysis.ResultsDuring the study period, there were 301 eligible patients who met the study criteria. Of those, 82 (27.24%) had WRF. There were two independent factors associated with WRF occurrence: baseline diastolic blood pressure and beta blocker treatment, with adjusted odds ratios (95% confidence interval) of 1.060 (1.008, 1.114) and 0.064 (0.006, 0.634), respectively. The Hosmer-Lemeshow Chi square for the final model was 6.11 (p = .634).  ConclusionsAfter examining several heart failure treatments and baseline factors, we found that beta blocker treatment results improvement in kidney function.     

Intravenous iron therapy in renal failure: friend and foe?

Anemia is a common feature of chronic renal dysfunction and is associated with significant morbidity and mortality. Although acquired insufficiency of erythropoietin is virtually universal, iron deficiency is also a common contributor to the development of anemia. Iron replacement, in particular via the intravenous route, has become commonplace and results in improved hematocrits either on its own or in association with an erythropoiesis stimulating agent. However, intravenous iron is not without its potential complications. These include acute allergic reactions, iron overload, potentially accelerated cardiovascular disease and risk of infection. It is the purpose of this review to critically evaluate the available clinical and experimental evidence linking iron supplementation therapy with these complications.     

Retroperitoneal abscess with consecutive acute renal failure caused by a lost gallstone 2 years after laparoscopic cholecystectomy

A 70-year-old male patient presented with abdominal pain, acute renal failure, and fever 2 years after laparoscopic cholecystectomy. During the surgical drainage of the abscess formation on the patient’s right flank, a huge gallstone was found in the retroperitoneum. The patient was dismissed from the hospital 11 days after admission with normal lab panel and restored renal function.     

Role for alkaline phosphatase as an inducer of vascular calcification in renal failure?

Vascular calcification is associated with increased cardiovascular morbidity and mortality. A number of calcification inhibitors have been defined recently, including inorganic pyrophosphate (PP(i)), an important physicochemical inhibitor of hydroxyapatite crystal growth. Increased hydrolysis of PP(i) by tissue-nonspecific alkaline phosphatase (TNAP) may occur in renal failure and act to enhance mineralization of vessels.     

Experimental models of acute renal failure and erythropoietin: what evidence of a direct effect?

The kidney can achieve a structural and functional recovery after the damage induced by ischemia and reperfusion. This is due to the regeneration of epithelial tubular cells, the intervention of immature cells mainly localized in the medulla, and a small number of bone marrow-derived stem cells. In many instances, however, recovery is delayed or does not occur at all. The mechanisms allowing the renal cells to de-differentiate still need to be clarified in order to find a therapeutic approach that can amplify this ability and then stop the fibroid involution and the progression toward renal failure. Several authors have hypothesized a protective effect of EPO against ischemic and cytotoxic renal damage and observed that patients precociously treated with EPO showed a slower progression of renal failure. EPO has been demonstrated to have proliferative and anti-apoptotic effects in ischemia-reperfusion models in the brain and cell cultures. Moreover, EPO can mobilize stem cells and increase the plasmatic levels and the renal expression of VEGF. These effects seem to be dose-dependent and could be due to the activation of signal transduction systems, like Jak and STAT. In the presence of high doses of exogenous EPO or during the treatment with long-acting EPO-like molecules, non-specific receptors may be activated through a low-affinity link. Further investigations are needed to determine new therapeutic applications for EPO and other analogous hormones. Very long-acting molecules or molecules with cyto-protective but no erythropoietic effect may represent useful tools in the study of the molecular mechanisms underlying EPO's action and may have a rapid and safe therapeutic application.