The future of hemodialysis membranes

Hemodialytic treatment of patients with either acute or chronic renal failure has had a dramatic impact on the mortality rates of these patients. Unfortunately, this membrane-based therapy is still incomplete renal replacement, as the mortality and morbidity of these patients remain unacceptably high. Much progress must be made to improve the biocompatibility of hemodialysis membranes as well as their hydraulic and permselective properties to remove small solutes and 'middle molecules' in compact cartridges. The next directions of development will leverage materials and mechanical engineering technology, including microfluidics and nanofabrication, to further improve the clearance functions of the kidney to replicate glomerular permselectivity while retaining high rates of hydraulic permeability. The extension of membrane technology to biohybrid devices utilizing progenitor/stem cells will be another substantive advance for renal replacement therapy. The ability to not only replace solute and water clearance but also active reabsorptive transport and metabolic activity will add additional benefit to the therapy of patients suffering from renal failure. This area of translational research is rich in creative opportunities to improve the unmet medical needs of patients with either chronic or acute renal failure.     

On short-term dialysis

The short-term dialysis occupies a medium position between the obligatory dialysis in patients with acute renal failure and the intermittent chronic dialysis in patients with irreversible renal diseases. By short-term dialysis many, eventually fatal, therapeutic errors may be avoided. In many cases, it is possible to gain time necessary for further diagnostic considerations in azotaemia of obscure origin, for overcoming the critical moments of exacerbation in chronic nephropathies and for obtaining a remission of variable duration. Thanks to the short-term dialysis, the condition of the patients in the preoperative period could be controlled, the surgical hazards reduced and the operative results improved. The performance of several dialyses permits a better selection of patients for chronic dialysis and renal transplantation and the avoidance of useless efforts to submit inappropriate patients to such a mode of treatment.     

The bioartificial kidney: current status and future promise

The rapid understanding of the cellular and molecular bases of organ function and disease processes will be translated in the next decade into new therapeutic approaches to a wide range of clinical disorders, including acute and chronic renal failure. Central to these new therapies are the developing technologies of cell therapy and tissue engineering, which are based on the ability to expand stem or progenitor cells in tissue culture to perform differentiated tasks and to introduce these cells into the patient either via extracorporeal circuits or as implantable constructs. Cell therapy devices are currently being developed to replace the filtrative, metabolic, and endocrinologic functions of the kidney lost in both acute and chronic renal failure. This review summarizes the current state of development of a wearable or implantable bioartificial kidney. These devices have the promise to be combined to produce a wearable or implantable bioartificial kidney for full renal replacement therapy that may significantly diminish morbidity and mortality in patients with acute or chronic kidney disease.     

Peritoneal dialysis in patients with heart failure

Both in dialysis patients and non-uremic patients heart failure is associated with an adverse prognosis. In a state of abrupt worsening of cardiac function, acute cardiogenic shock or decompensated congestive heart failure, acute kidney injury may occur, whereas in a more chronic worsening of cardiac function chronic kidney injury may occur. Recently, the term cardiorenal syndrome was adopted and defined as "a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ". Despite better treatment techniques and the continuous development of new medications volume overload in patients with cardiorenal syndrome is difficult to treat. Especially treatment of cardiorenal syndrome type I and II is notoriously difficult. Peritoneal dialysis might be, because of the gradual fluid removal, a therapeutic option in these patients. However, data on the effect of peritoneal dialysis in patients with heart failure with fluid overload and/or renal impairment are scarce. In this reviewe, the role of peritoneal dialysis in the treatment cardiorenal syndrome type I, II and IV will be discussed.     

Gastrin and gastric acid secretion in renal failure

In 10 anephric patients awaiting transplantation, 15 patients with chronic renal failure and 30 patients with acute renal failure, daily basal plasma gastrin levels and basal and stimulated gastric acid secretion were measured. Significant elevated plasma gastrin levels were found in all of the anephric patients and in 50 percent of the patients with acute and 55 percent of those with chronic renal failure. Elevated plasma gastrin levels decreased to normal after kidney transplantation or when kidney function returned to normal in the patients with acute renal failure. Gastric acid secretion studies showed a consistent pattern in all three groups of patients with a low basal acid output, a high basal intragastric pH and a very significant peak acid output, perhaps secondary to elevated plasma gastrin levels due to inadequate renal inactivation of gastrin. This may partly explain the increased incidence of gastrointestinal bleeding and gastritis seen in patients with different degrees of renal failure.     

The deceiving image: asymptomatic renal malakoplakia in a patient with chronic renal failure.

The diagnosis of tumour-like renal lesions may be difficultin chronic renal failure (CRF) patients. We present a patient with severe CRF, in whom the diagnosisof malakoplakia during intervention avoided nephrectomy, therebypreserving his residual renal     

Postoperative chronic renal failure: a new syndrome?

Of 125 patients with postsurgical acute tubular necrosis, 87 died, 34 regained clinical normal renal function, and 4 survivors (9.5%) were left with severe permanent renal failure, two of whom required chronic dialysis and transplantation. Preoperatively these 4 patients had normal renal function. The 4 patients were above age 60, two had undergone methoxyflurane anesthesia, and nephrotoxic antibiotics were used in all. The incidence of permanent renal failure is much higher than ever reported and may reflect the survival of patients who previously died because of less ideal dialysis. We believe that the cause of this permanent lesion is multifactorial, including age (over 60 years), nephrotoxic antibiotics (particularly cephalothin and gentamicin sulfate), and nephrotoxic anesthetic (methoxyflurane) agents. This combination of factors should be avoided whenever possible.     

Rhabdomyolysis and acute renal failure in chronic alcoholics with myopathy, unrelated to acute alcohol ingestion

Rhabdomyolysis leading to acute renal failure necessitating hemodialysis is described in three chronic alcoholics. In each case an acute medical or surgical event, but not alcoholic intoxication, was implicated. Renal biopsies demonstrated acute tubular necrosis with intraluminal deposits consisting of Tamm-Horsfall protein and myoglobin. After recovery all three patients were demonstrated to have proximal muscle weakness with similar electromyographic abnormalities but nerve-conduction was impaired in only two. Muscle biopsies showed mixed, but predominantly type II fiber atrophy and reduced muscle phosphorylase levels. In the one patient tested the lactate response to forearm muscle ischemia was abnormal. It is postulated that chronic alcoholics may be predisposed to rhabdomyolysis and acute renal failure following acute medical and surgical stress as well as acute alcohol abuse. The muscle damage in these patients may be due to impaired intra cellular glycogen metabolism.     

Bioartificial kidney for full renal replacement therapy

The rapid understanding of the cellular and molecular basis of organ function and disease processes will be translated in the next millennium into new therapeutic approaches to a wide range of clinical disorders, including acute and chronic renal failure. Central to these new therapies are the developing fields of gene therapy, cell therapy, and tissue engineering. These new technologies are based on the ability to expand stem or progenitor cells in tissue culture to perform differentiated tasks and to introduce these cells into the patient either in extracorporeal circuits or as implantable constructs. Cell therapy devices are currently being developed to replace the filtrative, metabolic, and endocrinologic functions of the kidney lost in both acute and chronic renal failure. This article summarizes the current state of device development for a renal tubule assist device, a bioartificial hemofilter, and a regulatable erythropoietin cell therapy device. These individual devices have the promise to be combined to produce a wearable or implantable bioartificial kidney for full renal replacement therapy. These new approaches may result in therapeutic modalities that significantly diminish the morbidity and mortality in patients with acute renal failure or end-stage renal disease.     

Recovery from Acute Renal Failure

Acute tubular necrosis is the most common cause of acute renal failure making up two-thirds of such cases. Mortality is best correlated to basic disease. Surgery, particularly in the abdomen, carries an unusually sinister prognosis. The influence of age on outcome is controversial. Intensified dialysis, early reoperations, hyperalimentation, and possibly continuous dialysis and antibiotic barrage deserves close investigation as tools of improving survival.

Almost all surviving patients recover renal function within 30 days and beyond two months recovery almost never occurs. Approximately 3% of the patients initially suspected of having acute tubular necrosis will need chronic hemodialysis indefinitely or have a transplant to regain renal function. The older patient seems to be more susceptible to this problem. Delayed recovery and chronic renal failure is unusual. High dose loop diuretic therapy and hyperalimentation with intravenous amino acids may shorten the time for recovery, although considerable controversy exists.     

Rhabdomyolysis: need for high index of suspicion

Rhabdomyolysis, both traumatic and nontraumatic, may be defined as a triad of skeletal muscle injury, pigmented urine, and acute renal failure. Nontraumatic rhabdomyolysis may be more of a subtle diagnosis and requires a high index of suspicion. Pertinent findings in the history as well as clinical evidence of muscle injury with a marked elevation of creatinine kinase will suggest the diagnosis. A disproportionate elevation of serum creatinine to blood urea nitrogen may also occur. Treatment consists of adequate hydration to help prevent oliguric or anuric renal failure without additional calcium or bicarbonate supplementation in most cases. Radiologic studies involving intravenous contrast media as well as urologic instrumentation should be avoided in the acute setting. With early diagnosis and prompt treatment the prognosis for recovery is excellent.     

Vascular access for dialysis in the intensive care unit

Management of the vascular access (VA) for renal replacement therapy (RRT) in acute renal failure (ARF) patients is faced with a twofold problem: first, the creation of an angio-access that is adequate for RRT in the acute setting; second, the preservation of the patient's vascular network in order not to preclude further use of the vessel in the event of evolution to chronic renal failure. Central venous catheters are the preferred VA for RRT in the intensive care setting. Semi-rigid double-lumen polyurethane catheters may be considered for short-time use (up to 2-3 weeks). Soft silicone double-lumen or twin-catheters, preferably with subcutaneous tunnelling, are highly desirable for prolonged RRT (over 3 weeks). The femoral route is the first option in the presence of associated risk factors (respiratory failure, pulmonary oedema, bleeding...). The internal jugular route should be considered for mid-term use in order to facilitate the patient's mobilization and to reduce the risk of infection. The subclavian route should be avoided because of the risk of stenosis and/or thrombosis of the outflow vein. Catheter insertion must be performed by a trained physician with ultrasound guidance using either skin mapping or continuous vein guidance. Catheter handling and care should comply with best practice guidelines and should be part of a continuous quality improvement programme in order to reduce catheter-related morbidity. Preservation of the upper limb vascular network of the patient consists of sparing the native vessels (artery and vein) of the patient and preserving the functionality of the permanent VA in chronic renal failure patient. This 'lifeline' of chronic renal failure patients may be maintained by preventing inflammation, infection and thrombosis of the superficial vessels of the arm and forearm of patient.     

Fluid and electrolyte problems in renal dysfunction

The primary function of the kidney is to maintain fluid and electrolyte homeostasis. Each day the kidney must excrete 1500 ml of water and any excess ingested sodium, potassium, magnesium and phosphate. The kidney also plays a key role in calcium homeostasis. Of the total number of patients in intensive care 3–25% will develop acute renal failure and patients with chronic renal disease will frequently present for surgery. The treatments for renal dysfunction may themselves cause disturbance in fluid and electrolyte homeostasis, particularly the use of diuretics and renal replacement therapy. Loss of normal renal function may lead to major changes in fluid and sodium balance. Volume status assessment will be required in patients with renal dysfunction because they are at risk of both hypovolaemia and hypervolaemia. Loss of renal function will lead to retention of potassium and magnesium with serious systemic and cardiovascular consequences including cardiorespiratory compromise and collapse and cardiac dysrhythmias. Hypocalcaemia will result from reduced renal calcitriol production and phosphate retention. The identification of fluid and electrolyte imbalances and the management of clinically significant changes are required when treating patients with renal dysfunction on an intensive care unit or who present for anaesthesia.     

Hot-topic debate on kidney function: renal-sparing approaches are ineffective

Key Points: 1. Both acute kidney injury and chronic renal disease are common in patients undergoing liver transplantation. The etiologies are mixed. 2. The incidence of chronic renal failure after liver transplantation is unacceptable, and it has a significant impact on long-term outcomes after liver transplantation. 3. The role of calcineurin inhibitors (CNIs) in the development of posttransplant chronic renal failure is likely overrated. 4. The use of CNIs in the early posttransplant period is currently essential. 5. Whether new agents will be able to provide effective immunosuppression as primary immunosuppressives remains to be proven.     

Acute renal failure - how and when to treat?

Acute renal failure is a common condition in intensive care units. The negative impact of acute renal failure on mortality has been demonstrated in recent studies. All critically ill patients should be regarded as a high risk population for renal failure. The optimization of intravasal fluid status and mean arterial pressure are preventive strategies in these patients. The use of nephrotoxic drugs (including radiocontrast media) should be avoided if possible. In cases of established acute renal failure today therapeutic strategies are still limited to best supportive care. The use of diuretics can facilitate fluid balance, however they seem to have an adverse effect on excretional renal function. A number of patients with acute renal failure need extracorporal renal support. Overload of potassium or fluids, severe acidosis, uremic pericarditis or uremic encephalopathy are urgent indications for the start of renal replacement therapy. Small randomized trials give some evidence that an early start of renal replacement therapy may be beneficial in critically ill patients. In this patient group renal replacement therapy should be considered when serum urea concentrations exceed 100mg/dl and/or when early signs of indications mentioned above are present. Large randomized multicenter trials have shown that a favourable effect on mortality can only be achieved when renal replacement therapy is supplied with a sufficient dose. Daily hemodialysis or continuous hemofiltration with a filtrate volume of 35ml/kg/h is regarded as a standard of care. There is still controversy whether continuous hemofiltration is superior to intermittent hemodialysis. Large meta-analyses could not show a difference in mortality with either one of the two therapy options.     

Acute deterioration of renal function associated with enteric hyperoxaluria

Enteric hyperoxaluria due to malabsorption syndromes has been well documented to cause renal calculi and chronic tubulointerstitial renal damage. Rarely, in the setting of intestinal bypass operations for morbid obesity, enteric hyperoxaluria has produced acute renal failure. We report two patients who suffered acute deterioration of renal function associated with increased intestinal absorption and renal excretion of oxalate associated with steatorrhea. One patient had a large portion of his small bowel resected many years prior to the onset of the renal failure and the second patient had chronic pancreatitis causing steatorrhea. Both patients had renal biopsy documentation of the acute nature of the tubular damage produced by oxalate deposition. The mechanisms of their deterioration of renal function may relate to sudden increases in steatorrhea in association with episodes of volume depletion. Enteric hyperoxaluria may be an easily overlooked and potentially preventable etiology of acute renal dysfunction.     

Decreased fractional excretion of urate as an indicator of prerenal azotemia

Although the fractional excretion of uric acid (FEUA) is known to reflect extracellular fluid volume changes, the diagnostic significance of decreased FEUA in dehydration has not been previously reported. We studied the possible association between low FEUA and acute prerenal azotemia, and its diagnostic value, compared with other traditional indices, in discriminating prerenal azotemia from renal parenchymal causes of acute renal failure. In 65 chronic renal disease patients, 174 FEUA measurements were obtained from 24-hour urine collections. FEUA levels increased as reciprocal serum creatinine levels decreased. All 8 patients with prerenal azotemia showed significantly decreased FEUA values compared with chronic renal disease patients with a comparable degree of serum creatinine elevation, whereas all 7 patients with acute renal failure had FEUA values higher than those of chronic renal disease patients with comparable creatinine levels. FEUA values in prerenal azotemia were distinctly lower than those in acute renal failure (p less than 0.001). Patients with prerenal azotemia showed a lower fractional excretion of sodium, a lower fractional excretion of chloride and renal failure index, and a higher urine-to-plasma creatinine ratio than those with acute renal failure (p less than 0.05). However, these traditional indices were not useful in discriminating between the two conditions. The urine-to-plasma urea nitrogen ratio and the ratio of plasma urea nitrogen to creatinine showed no statistical difference between prerenal azotemia and acute renal failure. We conclude that, in acute azotemia, a decreased FEUA value may represent a reliable indicator of prerenal azotemia in the differential diagnosis of acute renal failure.     

Acute renal failure in the elderly

Acute renal failure in elderly patients is common and likely to become more so as life expectancy in France continues to grow. The chances of acute renal failure occurring in the elderly are increased by changes in renal function and the effects of various chronic diseases such as diabetes, hypertension and obstructive urological disorders, all of which increase in incidence with age. The elderly may develop all types of the disease but are most prone to drug-related acute renal failure. The diagnostic and therapeutic strategies adopted are the same as those for adult patients but should take into account the potential risks and benefits in this specific age group. However, age should no longer be considered as the sole determining factor in diagnostic and therapeutic decisions. The elderly are among those who benefit most from preventive measures against acute renal failure.     

Dialysis in non-renal organ (liver) transplantation

The renal management of acute hepatic failure and liver transplantation requires an understanding of the features of liver failure and the causes of liver graft dysfunction. The management of any underlying pathology in addition to supportive care is fundamental to successful management and a return to independent renal function. These issues are discussed particularly in relationship to a case history involving a patient presenting with acute fulminant liver failure secondary to a paracetamol overdose who was successfully treated by liver transplantation and continuous veno-venous haemodiafiltration. The liver can be successfully transplanted but acute renal failure is a severe complication post-transplantation. Its appearance can be predicted in patients with pre-transplant renal dysfunction, severe graft dysfunction, or both. It may be avoided through careful selection of transplant recipients and correct timing of transplantation. Prevention of renal failure, appropriate patient selection for transplantation and timely procurement of a donor organ are vital for best use of limited donor resources. Treatment success depends on patient and donor selection, skilled surgeons, careful post-operative care, and successful immunosuppression.     

Malaria and acute kidney injury

Malaria is a major public health problem in tropical countries. About 500 million people suffer from malaria, leading to death in 1 to 3 million cases. Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. As per World Health Organization criteria, acute renal failure (serum creatinine level, > or =3 mg/dL or > or =265 micromol/L) occurs as a complication of Plasmodium falciparum malaria in less than 1% of cases, but the mortality rate in these cases may be up to 45%. It is more common in adults than children. Renal involvement varies from mild proteinuria to severe azotemia associated with metabolic acidosis. It may be oliguric or nonoliguric. AKI may be present as a component of multi-organ dysfunction or as a lone complication. The prognosis in the latter is generally better. Several pathogenic mechanisms interplay for the clinical manifestation. The predominant lesions are acute tubular necrosis and mild proliferative glomerulonephropathy. These patients do not progress to chronic kidney disease. The management of malaria-induced AKI includes appropriate antimalarials (parenteral artesunate or quinine), fluid electrolyte management, and renal replacement therapy at the earliest. The use of diuretics should be avoided.