The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome

Anemia is a major problem in patients with chronic kidney insufficiency. The development of recombinant human erythropoietin has enabled physicians to correct this anemia. Although anemia has not been considered to be a common or important contributor to congestive heart failure, anemia of any cause can lead to cardiac damage and eventually congestive heart failure. Our joint renal-cardiac heart failure team found that anemia was indeed very common in congestive heart failure and was associated with severe, medication-resistant cardiac failure. Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized. Subsequent investigations by others have confirmed many of our observations. We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome. Treatment of the anemia in congestive heart failure may prove vital in preventing progression of both the heart failure and the associated renal disease.     

Pure red-cell anemia due to recombinant human erythropoietin and its status in oncology practice

A special form of anemia was observed during the treatment with recombinant human erythropoietin having been applied for more than 15 years. The pure red-cell anemia due to antibodies against erythropoietin was described in chronic renal failure patients. Since oncological patients are also treated with rhuEPO it is interesting to know whether this side effect could be observed in the patients with solid tumors as well. It should be considered in tumorous patients when coexistence of antibodies against rhuEPO with pure red-cell aplasia is demonstrated, and its other causes as immunological disease, thymoma, viral infections (eg. Parvovirus B12, Hepatitis B or C) are excluded. The author collected literature data and found the absence of reports on this side effect in cases of treatment with rhuEPO in cancer patients. The rhuEPO treatment is a safe method for the cure of cancer anemia as antibodies against rhuEPO have not been shown together with PRCA among cancer patients. The possible explanation could be the shorter application time in cancer compared to the chronic renal failure patients. The side effect observed in chronic renal failure patients calls the attention to the precise compliance with the instructions of the manufacturers.     

The anemia of chronic renal failure: in vitro response of bone marrow to erythropoietin.

Bone marrow cells of patients with chronic renal failure were studied in short-term in vitro cultures to determine erythropietin responsiveness. Seven normals and fourtheen patients on hemodialysis were studied. Bone marrow cells of normal subjects and of patients with chronic renal failure responded similarly to erythropoietin. Total heme synthesis was significantly lower in cultures prepared with uremic serum than normal serum. We conclude that there is a substance in the serum of uremic patients which suppresses general heme synthesis and that this "uremic toxin" may be responsible, in part, for the clinically severe anemia seen in these patients.     

The dyslipidemia of chronic renal disease: effects of statin therapy

PURPOSE OF REVIEW: Dyslipidemia is a prevalent condition in patients with chronic renal disease, but is often left untreated. Statin treatment constitutes an effective way to improve lipid abnormalities. This review summarizes present studies on dyslipidemia and its treatment in patients with chronic renal disease. RECENT FINDINGS: The specific dyslipidemia in renal disease is associated with the presence of proteinuria and decreased creatinine clearance, and may even adversely affect the progression of chronic renal disease. Statin therapy may have renoprotective effects due to a combination of lipid lowering and pleiotropic effects. Statins exert several anti-inflammatory properties and lead to a decrease of proteinuria. Post-hoc analyses of large-scale lipid lowering trials have shown that the reduction of cardiovascular risk was equivalent to the reduction achieved in patients without chronic renal failure. We feel, however, that if intervention with statins is postponed until patients reach end-stage renal disease, statins have limited benefit. SUMMARY: Present studies suggest that patients with renal disease should be screened early for dyslipidemia and that statins have to be considered as the lipid lowering therapy of choice. These drugs reduce cardiovascular risk. Further studies are needed to firmly establish whether statins preserve renal function.     

Impaired renal function and aluminum metabolism

The consequences of renal functional impairment on aluminum (Al) excretion are not clear inasmuch as little is known about its glomerular filtration, tubular reabsorption, or secretion. The association of Al and the etiology of the dialysis encephalopathy syndrome and osteomalacia among patients with uremia suggests that renal functional impairment is a prerequisite for increased body Al stores. However, considerable evidence argues against the concept that tissue Al accumulation occurs as a simple consequence of renal failure. Many dialysis patients have high parathyroid hormone (PTH) concentrations that have been associated with neurologic abnormalities, bone disease, and anemia. The toxicity of PTH could be either direct or indirect by influencing the metabolism of potentially toxic substances such as Al. Our studies in normal rats suggest that gastrointestinal Al absorption and specific tissue burdens are enhanced by PTH, but not irreversibly, because the withdrawal of PTH resulted in Al egress. Dialysis patients are often treated with vitamin D analogs to prevent or control consequences of hyperparathyroidism and impaired 1,25-dihydroxycholecalciferol synthesis. Although some reports suggest that high bone Al in osteomalacia may be responsible for vitamin D resistance, our studies with normal rats suggest that its metabolites may also increase tissue Al burdens independent of PTH action. Thus, several factors operative in uremia other than impaired renal function may contribute to altered Al metabolism and, consequently, to its toxicity.     

Selective effect of low protein diets in chronic renal diseases.

It has recently been established that the rate of progression of chronic renal failure in man can be slowed by restricting dietary protein. Consequently, the short term and long term effects of a low protein diet on the course of different chronic nephropathies were studied in an attempt to delineate the factors that determine the response to such a diet. When a low protein diet was given for six months renal function improved significantly in nine patients with chronic tubulointerstitial nephritis (p less than 0.025); the diet had a marginally beneficial effect in 12 patients with chronic glomerulonephritis (p less than 0.05) and no effect in nine with hypertensive nephrosclerosis. The heterogeneous functional response in the patients with chronic glomerulonephritis correlated closely with the effect of the diet on these patients'' proteinuria (r = 0.76, p less than 0.01). In a short term study (four weeks) of 12 patients with chronic renal failure changes in renal plasma flow were proportional to dietary protein intake. Renal vascular resistance fell during a high protein diet and increased when dietary protein was restricted. The changes in renal plasma flow during the low protein diet correlated well with the patients'' long term functional response to the diet (r = 0.76, p less than 0.01). It is concluded that the response to a low protein diet in chronic renal failure is determined, firstly, by the nature of the underlying nephropathy, with maximal benefit being observed in non-glomerular disorders; secondly, by the effect of the diet on the proteinuria in chronic glomerulonephritis; and, thirdly, by the haemodynamic response to the diet, with patients with a reactive renal vascular bed improving with a low protein diet.     

Erythropoietin: current status

Understanding the regulation of red blood cell production has been greatly enhanced by the cloning and expression of the gene for human erythropoietin (Epo) and its receptor. The availability of recombinant human erythropoietin (rhEpo) for administration to patients has ushered in a new era in molecular medicine. Intravenous or subcutaneous administration of rhEpo can reliably cure the anemia of chronic renal failure and may be effective in the treatment of anemias secondary to chronic inflammation, malignancy, and marrow suppression from chemotherapy. In addition, rhEpo therapy will probably play a prominent role in transfusion medicine, both in preparing patients for auto-transfusions as well as in minimizing red cell transfusion requirements in the post-operative period.     

Cancer in patients receiving dialysis.

The incidence of cancer and related mortality was studied in 1651 patients from six dialysis centres in England over 10 years. The only type of cancer for which there was a significant excess was non-Hodgkin''s lymphoma (four cases observed against an expected incidence of 0.15 (p < 0.001); three deaths against an expected 0.1 (p < 0.001)). This excess could not be attributed to either subsequent transplantation or treatment with immunosuppressive drugs. Since immunodepression is a feature of chronic renal failure, these observations together with those on patints treated with immunosuppressive drugs suggest that immunosuppression favours the development of non-Hodgkin''s lymphoma. Studies in which it is concluded that patients receiving dialysis show an excess of other types of cancer have certain shortcomings; the unusual opportunities for detecting cancer in such patients may account for some of the reported excess.     

A cervical ligamentum flavum cyst in an 82-year-old woman presenting with spinal cord compression: a case report and review of the literature

Introduction

Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease.

Case presentation

A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. Legionella pneumophila serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically.

Conclusions

This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.     

Histological Reassessment of Three Kidneys Originally Described by Richard Bright in 1827-36

Portions of kidney from three patients with renal disease that were originally described by Richard Bright between 1827 and 1836 have been preserved in the Gordon Museum at Guy''s Hospital. Histological study has shown that two cases fall into the current diagnostic category of mesangiocapillary (membranoproliferative) glomerulonephritis. One of these patients had a five-year clinical history and died with chronic renal failure and uraemia. The other patient died after three to four months with a severe nephrotic syndrome. The third patient was a young woman with chronic “phthisis pulmonalis” and renal amyloidosis.     

Endothelin-1 in chronic renal failure and hypertension

Investigation into the role of endothelin-1 (ET-1) in renal function has revealed two major direct actions leading to the control of extracellular volume and blood pressure. These are the regulation of renal hemodynamics and glomerular filtration rate and the modulation of sodium and water excretion. In the rat remnant kidney model of chronic renal failure, ET-1 production is increased in blood vessels and renal tissues. These changes are related to an increase in preproET-1 expression and correlate with the rise in blood pressure, the development of cardiovascular hypertrophy, and the degree of renal insufficiency and injury. Selective ETA receptor blockade prevents the progression of hypertension and the vascular and renal damage, supporting a role for ET-1 in chronic renal failure progression. The increase in ET-1 production can be associated with other local mediators, including angiotensin II, transforming growth factor-beta1 and nitric oxide, the local production of which is also altered in chronic renal failure. In human patients with essential hypertension, atherosclerosis, and nephrosclerosis, plasma ET-1 levels are increased compared with patients with uncomplicated essential hypertension. Similarly, plasma ET-1 concentrations are markedly increased in patients with end-stage renal disease undergoing dialysis, and this correlates with blood pressure, suggesting that ET-1 may contribute to hypertension in these patients. The treatment of anemia in patients with renal failure with human recombinant erythropoietin increases blood pressure by accentuating the underlying endothelial dysfunction and the elevated vascular ET-1 production. Overall, these results support a role for ET-1 in hypertension and the end-organ damage associated with chronic renal failure. ETA receptor blockade may then represent a potential target for the management of hypertension and cardiovascular and renal protection.     

Recovery of olfactory function after nine years of post-traumatic anosmia: a case report

Introduction

Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case.

Case presentation

A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day). After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction.

Conclusion

Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated.     

Protective effects of plant-derived natural products on renal complications

Diabetic nephropathy is the leading cause of renal failure worldwide. This debilitating disorder has several underlying pathophysiologic mechanisms, and therefore a variety of pharmacologic agents have been developed to prevent or treat diabetic nephropathy; however, synthetic drugs may possess unfavorable side effects. In response to this, the global use of herbal-based pharmacologic agents is increasing among diabetic patients. Numerous studies have reported therapeutic benefits of herbal-based compounds against diabetes-induced renal dysfunction. These agents can prevent renal dysfunction and improve renal function by blocking or suppressing deleterious pathways such as oxidative stress, inflammation, apoptosis, necrosis, and nitric oxide deprivation that lead to vascular injuries. In the current study, we have reviewed the beneficial properties of the most common herbal agents used in renal complications and diabetic nephropathy.     

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.     

Effect of recombinant human erythropoietin on the anemia of chronic renal failure

Phase I and Phase II studies of recombinant human erythropoietin (rhEpo) were conducted in normal volunteers and in anemic patients with chronic renal failure on maintenance hemodialysis. Three hundred U/person of rhEpo was administered intravenously to healthy normal volunteers in the Phase I study, resulting in no subjective or objective changes. In the Phase II study, 66 patients with chronic renal failure on maintenance hemodialysis with less than 20% hematocrit values were treated with rhEpo in doses of 50 U/kg to 200 U/kg two or three times a week. Hematocrit values increased significantly during the 12 weeks, and the patients' conditions improved. Patients previously requiring blood transfusions became transfusion-independent during our study. There were no obvious side effects, thus indicating the safety and efficacy of rhEpo in the anemia of chronic renal failure.     

Safety issues of long-term glucose load in patients on peritoneal dialysis--a 7-year cohort study

Background

Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival.

Methods

We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox''s models with repeatedly measured time-dependent covariates.

Results

We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival.

Conclusions

Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients.     

Noninvasive positive-pressure ventilation in acute respiratory failure

Noninvasive positive-pressure ventilation is a type of mechanical ventilation that does not require an artificial airway. Studies published in the 1990s that evaluated the efficacy of this technique for the treatment of diseases as chronic obstructive pulmonary disease, congestive heart failure and acute respiratory failure have generalized its use in recent years. Important issues include the selection of the ventilation interface and the type of ventilator. Currently available interfaces include nasal, oronasal and facial masks, mouthpieces and helmets. Comparisons of the available interfaces have not shown one to be clearly superior. Both critical care ventilators and portable ventilators can be used for noninvasive positive-pressure ventilation; however, the choice of ventilator type depends on the patient''s condition and therapeutic requirements and on the expertise of the attending staff and the location of care. The best results (decreased need for intubation and decreased mortality) have been reported among patients with exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema.Noninvasive positive-pressure ventilation is the delivery of mechanical ventilation to patients with respiratory failure without the requirement of an artificial airway. The key change that led to the recent increase in the use of this technique occurred in the early 1980s with the introduction of the nasal continuous positive airway pressure mask for the treatment of obstructive sleep apnea. Studies published in the 1990s that evaluated the efficacy of noninvasive positive-pressure ventilation for treatment of diseases such as chronic obstructive pulmonary disease, congestive heart failure and acute respiratory failure have generalized its use in recent years.¹ In 1998, an international study on the use of mechanical ventilation found that 5% of patients admitted to intensive care units received noninvasive positive-pressure ventilation.²Noninvasive positive-pressure ventilation includes various techniques for augmenting alveolar ventilation without an endotracheal airway. The clinical application of noninvasive ventilation by use of continuous positive airway pressure alone is referred to as “mask CPAP,” and noninvasive ventilation by use of intermittent positive-pressure ventilation with or without continuous positive airway pressure is called noninvasive positive-pressure ventilation.     

Recurrent porphyria attacks in a Chinese patient with a heterozygous PBGD mutation

We report here the case of a 32-year-old Chinese Han woman who presented with frequent severe abdominal pain, convulsion, numbness and confusion. She also had hypertension, hyponatremia, chronic renal failure, anemia and a high urinary δ-aminolevulinic acid concentration. We identified a heterozygous splicing mutation in intron 11 (IVS11-2A → G) of the porphobilinogen (PBG) deaminase gene (PBGD) in her genomic DNA. This mutation had previously been reported in a North American patient, but was absent from 50 healthy Chinese controls.     

Puberty in chronically diseased patients

Delayed onset of puberty and a reduced pubertal growth spurt are often reported in patients suffering from chronic diseases. The basis of abnormal puberty in these patients is multifactorial. Nutritional deficiency may contribute to growth disorders and delayed puberty. Insufficient food supply and/or eating disorders and/or malabsorption of nutrients can be observed in these patients. Moreover, increased energy supplies are often needed in patients with chronic lung disease, infection or inflammation. More specific factors due to the disease itself may be involved in growth and puberty disorders. Abnormalities of the growth hormone (GH)-insulin-like growth factor (IGF)1 axis and gonadotrophin secretion have been described in patients with chronic renal failure, cystic fibrosis and Crohn's disease. More recently, it has been shown that cytokines produced during chronic diseases such as juvenile idiopathic arthritis may affect the GH-IGF1 axis. Finally, concomitant medication, namely corticosteroids, which are often given to these patients, may contribute to delayed puberty and poor pubertal growth.