Serum gastrin in patients with acute kidney failure

In 18 patients with acute renal failure and 11 patients with chronic renal insufficiency serum gastrin levels were estimated before and after a test meal. The results were compared with those obtained in a group of 52 healthy subjects. It was stated that patients with acute as well as chronic renal failure display a "physiological" increase of serum gastrin after stimulation by a test meal. In contrast to healthy subjects the post-test meal gastrin curves in patients with chronic and acute renal insufficiency during the anuric/oliguric phase started from significantly higher fasting values. From the results obtained it seems that diminished renal clearance of gastrin by the insufficient kidneys is only partially responsible for the elevated fasting values found in anuric/oliguric patients with acute renal failure or patients with chronic renal insufficiency.     

Pharmacotherapy for heart failure in patients with renal insufficiency

Clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and spironolactone improve survival in patients with heart failure. Because patients with heart failure and renal insufficiency have been underrepresented in these trials, little evidence is available to guide clinicians in the optimal management of patients with both conditions. Approximately one third to one half of patients with heart failure have renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2), and renal insufficiency is among the strongest predictors of mortality in patients with heart failure. Evidence supports the use of ACE inhibitors to improve survival in patients with moderate renal insufficiency (GFR, 30 to 60 mL/min per 1.73 m2), but there is little evidence with which to weigh the risks and benefits in patients with more advanced renal dysfunction. beta-Blockers improve survival in patients with heart failure, and their beneficial effect is unlikely to differ according to renal function. Spironolactone improves outcomes in patients with advanced heart failure, but renal insufficiency appears to increase risk for hyperkalemia and limits the use of the drug in patients with severe renal insufficiency. Future clinical trials in heart failure should include a representative number of patients with renal insufficiency to improve the evidence base and outcomes in this vulnerable population.     

Acute renal failure in patients with cirrhosis: perspectives in the age of MELD

In patients with cirrhosis, acute renal failure is mainly due to prerenal failure (caused by renal hypoperfusion) and tubular necrosis. The main causes of prerenal failure are "true hypovolemia" (induced by hemorrhage or gastrointestinal or renal fluid losses), sepsis, or type 1 hepatorenal syndrome (HRS). The frequency of prerenal failure due to the administration of nonsteroidal anti-inflammatory drugs or intravascular radiocontrast agents is unknown. Prerenal failure is rapidly reversible after restoration of renal blood flow. Treatment is directed to the cause of hypoperfusion, and fluid replacement is used to treat most cases of "non-HRS" prerenal failure. In patients with type 1 HRS with very low short-term survival rate, liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy (with terlipressin, noradrenaline, or midodrine [combined with octreotide]) may improve renal function in patients with type 1 HRS waiting for liver transplantation. MARS (for molecular adsorbent recirculating system) and the transjugular intrahepatic portosystemic shunt may also improve renal function in these patients. In patients with cirrhosis, acute tubular necrosis is mainly due to an ischemic insult to the renal tubules. The most common condition leading to ischemic acute tubular necrosis is severe and sustained prerenal failure. Little is known about the natural course and treatment (i.e., renal replacement therapy) of cirrhosis-associated acute tubular necrosis.     

Angiotensin- and norepinephrine-induced myocardial lesions: experimental and clinical studies in rabbits and man.

The ability of large doses of exogenous angiotensin II to cause widespread multifocal microscopic myocardial necrosis in the rabbit has been confirmed. Angiotensin II also consistently produced acute renal failure with, less consistently, renal tubular necrosis. Norepinephrine infusions caused histologically indistinguishable myocardial lesions, but did not detectably affect renal function or histology. Severe renal failure, induced by bilateral nephrectomy (with or without concurrent glycerol administration) was not associated with similar cardiac lesions. Acute renal failure of comparable or greater severity to that induced by angiotensin II was produced by intramuscular cephaloridine, and was not associated with cardiac lesions. Rabbits infused with saline intravenously or "sham"-operated by simply opening and closing the peritoneal cavity did not develop renal failure and showed no cardiac or renal lesions histologically. Myocardial lesions, apparently identical to those seen in the rabbits, were observed postmortem in three patients known to have had high circulating levels of angiotensin II before death, although in all three cases alternative explanations are possible. Unexplained arrhythmia, cardiac arrest, and central chest pain without clear cardiographic or serum enzyme evidence of myocardial infarction occurred in two other subjects with very high plasma levels of angiotensin II. These attacks ceased after bilateral nephrectomy and a consequent fall in plasma angiotensin II. The cardiac attacks in these five patients all occurred during or shortly after procedures, such as sodium-depleting dialysis, renal artery surgery, or diazoxide administration, known to cause increase in plasma concentrations of renin and angiotensin II.     

Effect of intrarenal furosemide on renal function and intrarenal hemodynamics in acute renal failure

The ability of short-term furosemide administration to alter intrarenal hemodynamics and to modify the clinical course of acute renal failure was assessed in six patients 2 to 9 days after the onset of acute renal failure. Following renal arterial catheterization, the intraarterial administration of furosemide at a dose of 9.6 mg/min for 30 minutes failed to improve renal function as assessed either by an increase in urine output or a decrease in serum creatinine during the 4 days after administration in the five oliguric patients. In a sixth patient with nonoliguric acute renal failure, urine volume increased with a gradual decrease in blood urea nitrogen and creatinine during the week after study. Furosemide failed to alter either mean renal blood flow or its intrarenal distribution as determined at intervals of 3 to 40 minutes after its infusion. These studies demonstrate that the short-term administration of furosemide in large doses does not improve renal hemodynamics or alter the clinical course of patients with established acute oliguric renal failure.     

Inotropic therapy for heart failure: an evidence-based approach

BACKGROUND: Agents that increase cardiac contractility (positive inotropes) have beneficial hemodynamic effects in patients with acute and chronic heart failure but have frequently led to increased mortality when given on a long-term basis. Despite this fact, inotropes remain commonly used in the management of heart failure. METHODS: We reviewed the available data on short- and long-term inotrope use in heart failure, emphasizing high-quality evidence on the basis of randomized trials that were powered to address clinical end points. RESULTS: Available data suggest that long-term inotropic therapy has a negative impact on survival in patients with heart failure, regardless of the agent used. The data that inotropic therapy improves quality of life are mixed. High-quality randomized evidence is lacking for the use of inotropes for other heart failure indications, such as for acute decompensations or as a "bridge to transplant." CONCLUSIONS: On the basis of the available evidence, the routine use of inotropes as heart failure therapy is not indicated in either the acute or chronic setting. Potentially appropriate uses of inotropes include as temporary treatment of diuretic-refractory acute heart failure decompensations or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Inotropes also may be appropriate as a palliative measure in patients with truly end-stage heart failure. A model of heart failure pathophysiologic features that combines an understanding of both hemodynamic and neurohormonal factors will be required to best develop and evaluate novel treatments for advanced heart failure.     

Renal function in advanced heart failure

Despite recent advances with neurohormonal antagonists and devices, the prognosis of patients with advanced heart failure (HF) remains grave. Renal dysfunction is a common comorbid condition in HF and is associated with adverse outcomes. Current evidence indicates that intrinsic renal disease and inflammation in HF makes the kidney susceptible to hemodynamic compromise and congestion and contributes to a great extent to the development of renal dysfunction. Relief of congestion requires combination treatment with diuretics, neurohormonal antagonists, and occasionally vasodilators as well as inotropes. However, high doses of diuretics may accelerate the development of renal dysfunction by increasing neurohumoral activity and inducing renal structural and functional changes. Ultrafiltration should be reserved for patients with true diuretic resistance. Finally, early identification of the "patient at risk" remains a challenging issue and is limited by the currently used conventional parameters of renal function. However, novel biomarkers of acute kidney ischemia and/or injury are emerging and promise to become a diagnostic option for this patient population.     

Interpreting the fractional excretion of sodium

In most normal subjects, the fractional excretion of sodium is usually less than 1 percent but may be raised with an increase in salt intake. In acutely azotemic patients, a low fractional excretion of sodium usually indicates a prerenal process that is responsive to volume repletion. However, such a low fractional excretion of sodium also can be seen with azotemia due to hepatic or cardiac failure, as well as acute glomerulonephritis, pigment nephropathy, contrast nephrotoxicity, polyuric renal failure associated with burns, acute obstruction, renal transplant rejection, and occasionally non-oliguric acute renal failure, none of which is a volume-responsive process. A fractional excretion greater than 1 percent in acutely azotemic patients usually indicates intrinsic renal injury, but is consistent with volume depletion in patients receiving diuretics or in some patients with chronic renal insufficiency. Similarly, a low quotient in acute renal parenchymal injury is usually interpreted to indicate widespread tubular integrity, but is consistent with several different pathophysiologic processes. The fractional excretion of sodium must be interpreted in light of the specific clinical setting and other laboratory data to be useful in patient management.     

The developing role of the renal diabetes nurse

Diabetes as a chronic disease is often complicated in its management, particularly when combined with chronic and end-stage renal failure. Patients, carers and health care professionals are unfortunately often confused by either too little or conflicting advice provided by the two specialist teams. Within this context, the Renal Diabetes Nurse (RDN) role serves to bridge the gap by ensuring effective links and communication. Currently, renal referrals are made from surrounding secondary care settings and primary care GP practices. The expansion of renal outreach clinics, the appointment of new consultant nephrologists and the emergence of nurse-led clinics, reflects our continuous growth to meet the demand for renal services. The number of patients with renal failure and diabetes is set to increase as the acceptance criteria are clarified and referral routes made explicit. An ageing population with 21-62% of the renal population over the age of 65 (depending on the location of the renal unit), coupled with an increase in the Asian and African-Caribbean population all contribute to increased patient numbers. It is now well recognised that these patients often experience associated generalised atheroma and vascular calcification from inadequately managed hypertension and diabetes over a number of years. Consequently, this group of patients are often "high maintenance" requiring input from the multidisciplinary team on a continuing basis.     

Renal dysfunction in acute and chronic heart failure: prevalence, incidence and prognosis

Most patients with heart failure have mild or moderate renal dysfunction. This reflects the combined impact of chronic renal parenchymal disease, renal artery disease, renal congestion and hypoperfusion, neuroendocrine and cytokine activation and the effects of treatments for heart failure. Remarkably, with good treatment, the average annual rate of decline in renal function is similar in patients with chronic heart failure and healthy people of a similar age. Urea appears to be a stronger marker of an adverse prognosis than creatinine-based measures of renal function. Recent evidence suggests that minor, transient increases in creatinine in the setting of acute heart failure are not prognostically important but persistent deterioration does indicate a higher mortality. The poor prognosis of patients with worsening renal function ensures that few require renal dialysis but this may change as methods to prevent sudden death improve and new ways are found to control fluid congestion. Reversing renal dysfunction and stopping its progression remain important targets for treatment of heart failure.     

Cellular immune response analysis of patients with leptospirosis

Peripheral blood mononuclear cells (PBMC) from acute leptospirosis patients with and without acute renal failure were studied in order to investigate the status of cellular immunity in this disease. We analyzed the lymphocyte subsets of leptospirosis patients by immunofluorescence and their responsiveness to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Additionally, we investigated the effect of the patients' sera on normal PBMC proliferative response. We observed a decrease in the CD3+ and CD4+ cell subsets in patients with and without acute renal failure, or in percentage values alone in those who had recovered from renal failure. An increase in the number of B lymphocytes was observed in all patients, compared with controls. This increase in B lymphocytes was seen even in patients who had recovered from renal failure, when the number of CD3+ and CD4+ lymphocytes had already returned to normal levels. The low PHA response observed only with lymphocytes from patients with acute renal failure suggests a suppressive effect. The proliferative response to PWM was comparable to controls, even in the patients with acute renal failure. This latter result and the expansion of the B cell number could be related to leptospiral-derived factor(s). We also showed that sera from patients with and without acute renal failure exerted some inhibitory activity on normal PBMC responses to PHA and PWM. Although the redistribution of lymphocyte subsets and the serum suppressor activity were related to acute renal failure and leptospiral factor(s), we suggest that the cellular immune system was not irreversibly affected, which is compatible with the good prognosis seen in the patients studied.     

The Use of Diuretics in Varying Degrees of Renal Impairment: An Overview

Administration of diuretics during acute renal failure in animals has been demonstrated to be of value with mannitol and/or loop-blocking diuretics, furosemide or ethacrynic acid. There is evidence that if these drugs are given very early in the controlled experimental environment that there will be some beneficial effect in maintaining renal function. However, in man the temporal relationship between the acute onset and the successful response to the administration of the drugs is, at best, coincidental and the use of diuretics in acute renal failure may not produce the same results as seen in the laboratory. One of the best guides to the underlying disease when there is acute decompensation in renal function is the utility of the renal failure index which utilizes urine and plasma sodium and urine and plasma creatinine ratios.

Large doses of loop-blocking diuretics can be of benefit in patients with mild to moderate chronic renal insufficiency and fluid retention and/or hypertension. When renal insufficiency is severe in the pre-dialysis setting, furosemide, bumetanide or muzolimine may be of some benefit; however, as renal failure worsens the response of the kidney is sluggish and it is wise to begin to dialyze when glomerular filtration deteriorates below 5 ml per minute.     

Pleiotropic renal actions of erythropoietin

CONTEXT: Erythropoietin (EPO), which is used clinically as recombinant human EPO (rHuEPO) for anaemia associated with end-stage renal failure and cancer chemotherapy, also has pleiotropic properties. Although EPO and its receptor are primary mediators of the normal physiological response to hypoxia, rHuEPO can provide impressive protection against acute ischaemic injury in several organs and tissues. The longer-acting hyperglycosylated derivative of EPO, darbepoetin-alpha, is also used for anaemia and has pleiotropic properties. However, the ability of EPO or its analogues to act directly to reduce the severity of renal injury associated with chronic renal failure is not known. STARTING POINT: Ferdinand Bahlmann and colleagues (Circulation 2004; 110: 1006-12) investigated whether low-dose subcutaneous darbepoetin-alpha could protect against renal dysfunction and injury in rats with induced chronic renal failure. Given once weekly, the drug improved renal function and reduced histological evidence of renal injury. Treated rats also had greater weight gain than controls, with no change in systemic blood pressure. The drug did not increase packed-cell volume and it improved survival. WHERE NEXT?: Although the pleiotropic actions of rHuEPO can ameliorate ischaemic and nephrotoxic acute renal failure, Bahlmann's work is the first evidence that darbepoetin-alpha reduces the renal dysfunction and injury of chronic renal failure. Thus rHuEPO and its analogues might have a use in patients with different types of renal failure. These pleiotropic actions, seen at lower doses, must be separated from the haemopoietic properties that occur at clinical doses and which, at the highest doses, might lead to unwanted effects. Novel analogues of EPO are devoid of haemopoietic activity but still possess protective properties. Their ability to reduce renal injury and dysfunction awaits investigation.     

Troponins and chronic renal failure in dialysis patients

Cardiovascular disease is a major cause of morbidity and mortality in dialysed patients with chronic renal failure. The diagnostic and prognostic value of cardiac troponin T (TnTc) and I (TnIc) has been questioned in this setting. Dialysed chronic renal failure patients often have raised TnTc and TnIc in the absence of acute ischaemic symptoms. This increase is the consequence of minor myocardial damage due to coronary artery disease, left ventricular hypertrophy and endothelial dysfunction. Abnormal catabolism and differences in the liberation or detection of bound or free forms of the troponins may also contribute to the finding of raised TnTc in asymptomatic chronic renal failure patients. In this population, TnTc has a better prognostic value than TnIc for the identification of patients at greater risk (mortality). Increased TnTc in asymptomatic dialysed chronic renal failure justifies a thorough cardiovascular work-up to diagnose ischaemia, left ventricular hypertrophy (which should be a target for treatment) and left ventricular dysfunction, especially in diabetic renal failure and when non-emergency surgery or renal transplantation are planned. The troponins (mainly TnTc) retain their value for stratification of risk in acute coronary syndromes of patients with renal failure. An invasive strategy and pharmacological treatment (at adapted doses), identical to those considered for patients with normal renal function, should be discussed in dialysis patients with chronic renal failure admitted for acute coronary syndromes with raised troponins.     

Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril.

OBJECTIVES--To investigate the role of prostaglandins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostaglandin synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure. DESIGN--Randomised, double blind, placebo controlled studies. Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by "open" intravenous infusion of prostaglandin E2 (study A). In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before "open" captopril (study B). METHODS--Blood pressure was measured using a mercury sphygmomanometer. Cardiac output was determined by Doppler interrogation of blood flow in the ascending aorta and echocardiographic measurement of aortic root diameter. Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit, and glomerular filtration rate by endogenous creatinine clearance. Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges. The concentration of plasma prostaglandin E2 was measured by radioimmunoassay. SETTING--University department of cardiovascular medicine. PATIENTS--12 patients with chronic stable heart failure before starting treatment with angiotensin converting enzyme inhibitors. RESULTS--Indomethacin resulted in adverse effects on cardiac output, systemic vascular resistance, renal blood flow, glomerular filtration, urinary sodium excretion, and calf vascular resistance. Changes were reversed with infusion of prostaglandin E2. Pretreatment with indomethacin resulted in the attenuation of the acute increase in cardiac output and decrease in systemic vascular resistance that occurred with captopril. Similarly, an increase in renal blood flow with captopril was attenuated by indomethacin. CONCLUSIONS--The acute adverse effects of indomethacin on central and peripheral haemodynamic and renal function suggest that prostaglandins have a significant role in the regulation of peripheral blood flow and renal function in patients with stable chronic heart failure. The attenuation by indomethacin of captopril induced improvements in haemodynamic function and renal blood flow is consistent with the hypothesis that captopril may act in part via an increase in prostaglandin synthesis.     

Diuretika bei Herzinsuffizienz

Diuretics are useful and inevitable in acute congestive heart failure with pulmonary congestion and edema. The use of low-dose thiazide diuretics is well established in arterial hypertension. In acute heart failure, diuretics are recommended for the treatment of fluid overload and pulmonary edema. No evidence is available so far regarding any benefit of diuretics on the outcome of patients with chronic heart failure, whereas evidence-based blockade of the renin-angiotensin system and sympathetic nervous system reduces the risk of congestion and improves survival. Several types of diuretics are relevant: loop diuretics, thiazides, and potassium-sparing diuretics. All diuretics have significant side effects, mainly electrolyte disorders, metabolic acidosis/alkalosis, insulin resistance, and ototoxicity. Diuretics have no benefit in acute or acute-on-chronic renal failure; moreover, they even increase mortality and reduce the chance of renal recovery in these patients. Increased mortality with the use of diuretics also seems to be associated with a higher risk of lethal arrhythmias. Sequential tubular blockade may be useful for the short term in potentiating the natriuresis in renocardiac syndromes. Furthermore, ultrafiltration or renal replacement therapy may have an additional beneficial effect in these patients, although controlled trials are still lacking.     

Acute renal failure following snakebite.

Eight patients with acute renal failure following snakebite were studied. Intravascular hemolysis and disseminated intravascular coagulation contributed to the development of acute renal failure in 6 patients. Direct nephrotoxicity causing acute renal failure is postulated in 2 patients, 1 of whom also revealed evidence of mild, disseminated intravascular coagulation. Three patients had histopathological lesions of acute symmetrical cortical necrosis and 3 had acute tubular necrosis. In 1 patient with acute tubular necrosis, in whom direct nephrotoxicity seemed to be responsible for renal failure, the striking histological feature was a uniform debasement and disappearance of tubular epithelium. In 2 patients with a clinical course of acute tubular necrosis, histological lesions could not be documented. All the 5 patients with acute tubular necrosis regained full recovery of renal function, 3 of them with the help of dialysis and 2 with conservative management. None of the 3 patients with acute cortical necrosis survived in spite of intermittent dialysis therapy.     

WHY THE PERSISTENTLY HIGH MORTALITY IN ACUTE RENAL FAILURE ?

Data from 109 patients in established Summary acute renal failure, referred during the period January, 1969, to April, 1971, have been analysed. Mortality in this group of patients was distressingly high (57%) despite intensive dialysis and intensive general care. Sepsis still remains a major problem both as a precipitating and complicating factor in acute renal failure. Milder forms of renal failure were rarely referred to the unit during this period; most patients being older, more severely ill, and with prolonged oliguria. Since mortality increases with age, irrespective of precipitating cause, the greater age of the series probably accounts for much of the high mortality. Survival from acute renal failure in old patients who had just had surgical operations was rare, and it is in this area that most remains to be done. 29 patients with urine hypo-osmolar or isoosmolar plasma were given frusemide 500 mg. or 250 mg. intravenously; only 7 showed a diuresis, and this was sustained in only 3.     

Renal Biopsy Findings in Acute Renal Failure in the Cohort of Patients in the Spanish Registry of Glomerulonephritis

Background and objectives: Renal biopsy in acute renal failure of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. This study analyzed the frequency and clinicopathologic correlations of renal native biopsied acute renal failure in Spain during the period 1994 through 2006.Design, setting, participants, & measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly.Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group.Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure.The study of the epidemiology of biopsy-confirmed renal disease provides useful information about the prevalence of renal disease and its clinical manifestations. Although there are several renal biopsy registries around the world, most describe the distribution of histopathologic findings, and very few analyze in detail the main clinical pictures that indicate renal biopsy, yet knowledge of the epidemiology of renal syndromes is of paramount importance in clinical nephrology.The Spanish Registry of Glomerulonephritis has recorded individual patient data for all renal biopsies performed since 1994 (1,2). This information enables us to study the epidemiology of renal syndromes and histopathologic data. Renal biopsy in acute renal failure (ARF) of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. In this report, we analyze the frequency and clinicopathologic correlations of renal native biopsied ARF in Spain during the period 1994 through 2006.