Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.     

The pathogenesis and consequences of AGE formation in uraemia and its treatment

Advanced glycation endproducts (AGEs) accumulate in uraemia as a consequence of diminished clearance of low molecular weight forms which retain their reactivity and may subsequently combine with circulating and tissue macromolecules. Successful renal transplantation is the only form of renal replacement therapy which effectively clears these circulating AGEs; both haemodialysis and peritoneal dialysis are comparatively ineffective although high-flux haemodialysis confers some benefits. De novo AGE formation may be accelerated in uraemia due to carbonyl and oxidative stress leading to further accumulation. The consequences for the patient with chronic renal failure may be acceleration of vascular disease, renal failure progression and dialysis-related amyloidosis. Accelerated peritoneal AGE formation as a consequence of treatment with peritoneal dialysis fluids may be detrimental to peritoneal membrane function but does not appear to contribute to systemic elevation of AGEs.     

Patients surviving more than 10 years on haemodialysis. The natural history of the complications of treatment

BACKGROUND: The purpose of this survey was to describe the natural history of complications in 52 long-surviving haemodialysis patients to obtain a clearer picture of the impact these patients have on the dialysis population. This is important as they are often no longer suitable for transplantation and therefore are destined to remain on dialysis for the rest of their lives. METHODS: The patients who survived for more than 10 years on haemodialysis alone were studied. Information was obtained from patients' records and from the renal unit computer. RESULTS: Mean age at start of dialysis was 43 years and mean duration of HD 14.5 years. Renal failure was most commonly due to polycystic kidney disease or glomerulonephritis. Sixty-two per cent of patients developed cardiovascular disease, 78% complained of joint pains, 72% had a parathyroidectomy, and 50% developed carpal-tunnel syndrome. Two hundred and forty-five episodes of infection were recorded, 41% related to vascular access acquired in hospital or on immunosuppression. Only three infections occurred which could be described as opportunistic. Twelve patients were hepatitis C positive. In the 37 patients who have died, cardiovascular disease was the most common cause of death. Compared to other patients who started on dialysis before 1986 but who had a successful transplant the survival of patients on haemodialysis is much worse. CONCLUSION: Long-term survival on renal replacement therapy is dependent on successful transplantation. Complications, morbidity, and mortality are high after 10 years of dialysis.     

Perspectives of end stage renal failure therapy in Singapore

Haemodialysis in Singapore started in 1961 when a patient with kidney failure was dialysed using the twin coil artificial kidney. Over the years, we have seen various new techniques like rapid high efficiency dialysis, haemodiafiltration (HDF) and rapid high flux HDF introduced. Dialysers with newer membranes have improved solute transport, biocompatibility and water removal. Mini heparinisation and heparin-free dialysis have circumvented problems of bleeding in high risk patients. Technological advances in haemodialysis will continue with more new modalities introduced. Newer forms of vascular access through the subclavian and internal jugular veins have phased out the use of chronic arterio-venous (AV) shunts. Continuous ambulatory peritoneal dialysis (CAPD) was introduced in 1980. This has been a boon for cardiac and diabetic patients. The initial problems with peritonitis are now manageable with our current rate of 24.1 patient months compared to 13.2 patient months in 1983. This has been achieved through the use of ultraviolet (UV) germicidal exchange device and transfer tube changes by trained nursing personnel as well as better patient training and education. New techniques have included the "O" disconnect set, the use of 2.5 litre dialysate, low calcium dialysate and the introduction of continuous cycling peritoneal dialysis (CCPD). Future focus will be on the problems of nutrition and protein loss. Renal transplantation remains the ideal renal replacement therapy. Cadaveric renal transplantation was initiated in 1970 and living related donor transplant in 1976. From 1970-1985, immunotherapy was azathioprine-based and from 1985, cyclosporin A (CyA) was introduced. CyA has abrogated many immunological risk factors. Preformed cytotoxic antibodies are still important.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anticardiolipin antibodies in hemodialysis patients and in renal transplant recipients: prevalence and significance

Increased anticardiolipin antibodies (aCL) serum levels have been recently described in haemodialysis patients and in renal transplant recipients, with a prevalence ranging from 4.8 to 46.4%. The causes and the clinical significance of aCL positivity in these patients are uncertain. We measured IgG- and IgM-aCL serum levels in 61 haemodialysis patients, in 14 renal transplant recipients and in 38 healthy controls. Increased levels of IgG-aCL were found in 4 haemodialysis patients (6.55%), in 2 transplant patients (14%) and in 2 of the healthy controls (5.26%). IgM-aCL serum levels were normal in all the patients. After one year of follow-up, no vascular events have been observed in aCL positive patients. It is probable that the presence of aCL in the serum of patients with end-stage renal disease is only an epiphenomenon and does not play a pathogenetic role.     

Risk factors of stroke in carotid endarterectomy

A case of acquired perforating dermatosis associated with diabetic nephropathy is described. The case is unusual in that the dermatosis first developed approximately 1 year after renal transplantation rather than at a time when renal function was more severely impaired or during haemodialysis. There was a partial response to treatment with isotretinoin but the use of this drug was limited by the development of hyperlipidaemia. The relevant literature is reviewed.     

Advances in the clinical management of pediatric kidney transplantation

Renal transplantation is the best form of renal replacement therapy for children reaching end-stage renal failure. The first human transplantation was performed by Dr. Voronoy from a cadaver donor in 1933; however, because of the lack of immunological laboratory assessments, this transplantation resulted in rejection. Progress in immunological evaluation and new immunosuppressive drugs have improved survival in renal transplantation. The first renal transplantation in Turkey was performed by Dr. Haberal et al. on November 3, 1975. This child was one of five siblings with juvenile nephronophytisis, and the mother was the donor. Dr. Haberal has thus pioneered renal transplantation in Turkey. In the following years Dr. Haberal initiated cadavral transplantation in our country in collaboration with Eurotransplant. He has also contributed to the law concerning transplantation in Turkey. Subsequently many transplantation centers have been developed in the country. In spite of marked progress in transplantation technology, pediatric transplantation has not improved as fast as adult transplantation. This is due to several factors, such as the difference in the etiological factors leading to chronic renal failure, technical factors, growth and sexual development, factors relevant to infections and vaccinations, and psychological problems.     

Global tuberculosis challenges

The authors report the case of a 49-year-old, insulin-dependent diabetic man treated by double kidney-pancreas transplantation. A T3, N3, M0 testicular tumour was discovered at the 8th month and treated by inguinal orchidectomy and 2 courses of chemotherapy. Immunosuppressant treatment was decreased without any consequences for the transplants. Seven years later, the patient was cured but still treated by haemodialysis for chronic rejection of the renal transplant. The pancreatic transplant was still functional and the patient is waiting for a second renal transplantation.     

Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone

An analysis of the factors that influence the increase in plasma immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) concentration in chronic renal failure showed that: (a) the increase correlated with the increase in serum creatinine concentrations; (b) beta-MSH was not cleared from the plasma by haemodialysis; (c) beta-MSH concentrations increased with length of time on dialysis and increased further after bilateral nephrectomy but there was no further increase with time; (d) beta-MSH levels decreased to normal after renal transplantation; and (e) beta-MSH was excreted in urine only when plasma levels rose to well above those of chronic renal failure (in Nelson's syndrome). These findings suggest that the kidney regulated plasma beta-MSH by a non-excretory mechanism and is the major site of beta-MSH metabolism.     

Chronic renal failure and sexual functioning: clinical status versus objectively assessed sexual response

BACKGROUND: Sexual dysfunctions are common among patients with chronic renal failure. The prevalence was assessed in a population of 281 patients (20-60 years), and it was attempted to determine whether their mode of treatment (haemodialysis, peritoneal dialysis, or kidney transplantation), or biochemical and endocrine variables and neuropathy affect sexual functioning. Patients with rheumatoid arthritis served as a comparison group. METHODS: Assessment included clinical history, physical and laboratory examinations, questionnaires measuring erotosexual dysfunctions, and a psychophysiological test procedure. The latter is a laboratory method which measures, in a waking state, subjective and physiological sexual arousal. RESULTS: Men on haemodialysis or peritoneal dialysis suffered significantly more often from 'Hypoactive Sexual Desire Disorder', 'Sexual Aversion Disorder' and 'Inhibited Male Orgasm' than men with kidney transplantation or rheumatoid arthritis. Interestingly, the prevalence of 'Male Erectile Disorder' did not differ significantly between the four groups and ranged between 17 and 43%. Of the women, transplanted patients suffered significantly less from 'Hypoactive Sexual Desire Disorder' than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Although 'Male Erectile Disorder' and 'Female Sexual Arousal Disorder' had a relatively high prevalence there were no differences in the four groups of patients in genital responses during psychophysiological testing. Genital responses during psychophysiological assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/ absence of neuropathy. CONCLUSION: The prevalence of sexual dysfunction was high. Sexual dysfunction in men on haemodialysis or peritoneal dialysis was not so much due to erectile failure but largely to loss of sexual interest, subjectively ascribed to fatigue. The latter was also found in women on haemodialysis or peritoneal dialysis.     

Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography

Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient was also found to have type II mixed cryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy.     

Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide

Renal transplantation therapy performed for amyloid nephropathy is controversial because of the fatal effects of the disease. Amyloidosis is a relatively frequent disease and is generally associated with familial Mediterranean fever (FMF) in Turkey. Renal transplantation in the treatment of amyloid nephropathy started in January 1985. Till now, 18 (3.2%) renal transplantations have been performed on patients who had amyloid nephropathy. The mean follow-up period was 34.6 months. Fourteen renal grafts still function well (creatinine: 1-3.2 mg/dL). The overall 1-year patient and graft survival rates were 88.9% and 83.0%, respectively. These rates are not statistically different from renal transplantations done for other cases of renal failure. Therefore, patients with end-stage renal failure due to amyloidosis can be considered as appropriate candidates for renal transplantation.     

Posttraumatic acute renal insufficiency

Acute renal insufficiency is a severe, but most frequent reversible illness followed by sudden onset, oliguria or anuria of indefinite duration, by rapid increase in decomposition products of protein catabolism in serum, by acidosis and fluid balance and electrolytes disorder. The aetiologic factors of acute renal insufficiency are various. A very significant aetiological factor in the appearance of acute renal insufficiency is a trauma caused by any kind or type of weapons, arms or instruments [1-5, 6, 9-13, 15]. Of a total number of injured persons who were treated in our institution (4,086 injured persons), 251 (6.14 percent) were with acute renal insufficiency, and of that number with all signs and symptoms of acute renal insufficiency 37 (0.9 percent) were treated with haemodialysis. Of the number of dialysed patients 30 (80 percent) patients had oliguric form of acute renal insufficiency and 7 (19 percent) were with non oliguric form of acute renal insufficiency. The most frequent injuries were to abdomen and then to extremities, liver, chest and kidneys. The smallest percentage concerned isolated injuries in extremities. According to a pathogenic mortality mechanism, the highest mortality was in patients with haemorrhagic syndrome and in septic condition, and the minimal in patients with other syndromes, such as crush syndrome, etc. In 25 (68 percent) patients acute renal insufficiency was associated with haemorrhagic syndrome, in 7 (18.9 percent) with crush syndrome and in 5 (13.5 percent) with septic condition. In 36 (97 percent) patients haemodialysis was performed and in 1 (3 percent) subject peritoneal dialysis. The reason for such a small number of peritoneal dialysis are severe injuries to abdomen and chest, since this type of dialysis could not be performed for technical reasons. In 27 (73 percent) patients haemodialysis was performed as a type of intermittent heparinization. In 5 (14 percent) patients heparinization was a type of continual heparinization. Thanks to prompt haemodialysis together with medical therapy and surgical treatment, the mortality rate in our patients was lower in comparison to mortality rate in other centres (Table 3). The main causes of acute renal insufficiency in our patients were: Acute tubular nercosis, peripheral blood flow insufficiency (hypovolaemia, cardiovascular failure), and postrenal insufficiency (excretory obstruction, intrarenal obstruction, urinary organ ruptures, haemorrhagic shock) and the underlaying kidney disease. Acute renal insufficiency can be divided into acute renal insufficiency, primary parenchymal renal insufficiency and postrenal azotaemia [1-6, 9, 12, 13]. During the therapy of these patients it is important to evaluate the dehydration degree of patients by clinical and laboratory parameters. In case of hypovolaemia the complete compensation of fluid should consist of infusion together with administration of diuretics. The central venous pressure should be maintained at the values in a range from 6 to 8 cm H2O. In case of oliguric acute renal insufficiency the fluid intake should be equal to diuresis plus every other loss of fluids. Diet should be high-caloric with carbohydrates in the amount of 100 mg, and that amount should be given three to four times daily (both parenterally and orally) together with restriction of potassium intake due to a well known effect of potassium on myocardium function. Dosage of drugs which are eliminated via kidney should be managed promptly by parenteral administration of antibiotic agents [7, 8, 13-16]. Haemodialysis should be started at the very beginning of the patients admission to the hospital and should be associated with anticoagulant therapy for avoiding haemorrhages. Thanks to haemodialysis performed in time, the mortality rate in our patients was reduced in comparison to health centres where haemodialysis was delayed. Thanks to such treatment of patients with many severe injuries in whom the mortality rate is usuall     

Antimicrobial prescribing in patients on haemofiltration

Continuous haemo(dia)filtration techniques as a means of extracorporeal renal replacement therapy are being used more and more, especially on intensive care units. The effect of intermittent haemodialysis on the pharmacokinetics of systemic antibiotics is well documented and advice is provided in the drug data sheets regarding dosage, timing and additional doses (post haemodialysis). Continuous haemofiltration significantly alters the handling of these same antibiotics compared with haemodialysis, such that if the advice given for 'haemodialysis' is used for patients on haemofiltration, under-dosing the patient may lead to sub-therapeutic antibiotic levels. The reasons for these differences are discussed and suggested dosage modifications are given for commonly used antimicrobials based on available published data.     

In vivo and in vitro diclofenac sodium evaluation after rectal application of soft gelatine capsules enabling application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) for controlled release

BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are at risk for the development of end-stage renal failure from the treatment of localized renal cell carcinoma. Transplantation with its attendant immunosuppression may predispose patients to tumor recurrence; however, there is little information regarding the outcome with this approach. In this article, we review the North American and European experience with renal transplantation in this patient population. METHODS: The study group comprises 32 patients who have VHL rendered anephric secondary to localized renal cell carcinoma and who have undergone renal transplantation. Patients were identified from North American (n=18) and European (n=14) registries. The outcome of the study group is compared with a cohort of 32 renal transplant recipients without VHL from the Cleveland Clinic Unified Transplant Data Base, who were matched for donor source, gender, age, transplant status (primary vs. regraft), and date of transplantation. RESULTS: The 23 men and 9 women in the study group received transplants between 1974 and 1996. The average age at transplantation was 36 years, and the average duration of dialysis before transplantation was 26 months. Patients have been followed for 48+/-35 months. There was no statistically significant difference in graft survival, patient survival, or renal function between the study and control groups. There were five deaths in both the study and control groups. In the study group, three patients died with metastatic disease. There was no difference in the duration of dialysis before transplantation between patients who developed metastatic disease and those who did not. CONCLUSION: These data support the utility of renal transplantation as an effective form of renal replacement therapy in this unique population, with a limited risk of recurrent cancer.     

Renal vein thrombosis as the major cause of renal failure in familial Mediterranean fever

Eighteen out of 57 patients (31-6 per cent) suffering from Familial Mediterranean Fever (FMF) were found to have the nephrotic syndrome, histologically proven amyloidosis and progressive renal failure. In 14 cases renal function deteriorated rapidly after the first appearance of significant proteinuria, and 12 cases (66-7 per cent) required regular haemodialysis. Seven of these patients, seen in the early stages of renal impairment, were subsequently diagnosed clinically as probably having developed renal vein thrombosis. There was radiological proof of intrarenal or major renal vein occlusion in five which in one patient progressed to inferior vena cave obstruction. Treatment with heparin, plasminogen activators and fibrinogenolytic agents was disappointing although renal function has stabilized in one patient on long term oral anticoagulant therapy. It is suggested that renal vein thrombosis is common in FMF with renal amyloidosis and usually causes rapid deterioration of function and irreversible renal failure requiring dialysis. Renal phlebography may delineate clot in the main renal veins or indicate areas of reduced blood flow due to thromboses in intrarenal venules. Treatment is only partially satisfactory but there is some evidence to suggest that renal phlebography should be undertaken promptly when renal function begins to fall followed by anticoagulant therapy to prevent further thromboembolic complications.     

Effect of correction of acidosis on nutritional status in dialysis patients

Malnutrition is a well-recognised feature of end-stage renal failure and contributes to the continuing high morbidity and mortality in this group of patients. One of the aetiological factors is metabolic acidosis which has been shown to increase protein degradation in both experimental models of chronic renal failure and in humans with uraemia. Many patients currently receiving haemodialysis have subnormal values of plasma bicarbonate. However, the values can be normalised by using a dialysate bicarbonate concentration of 35-40 mmol/l and in continuous ambulatory peritoneal dialysis (CAPD), a similar increment in plasma bicarbonate can be achieved using a dialysate lactate content of 35-40 mmol/l. In short-term studies in haemodialysis patients there is evidence of an increase in body weight and other anthroprometric parameters when the plasma bicarbonate has been normalised by increasing the dialysate bicarbonate content. A long-term study in CAPD patients has demonstrated increased body weight, tricep skinfold thickness and midarm muscle circumference in those patients with a plasma bicarbonate of 27.2 +/- 0.3 mmol/l, compared to those with a value of 23.0 +/- 0.3 mmol/l. These studies strongly suggest that correction of acidosis by increased dialysate buffering capacity will improve nutritional status for patients with end-stage renal failure.     

What is the place of peritoneal dialysis in the integrated treatment of renal failure?

The role of peritoneal dialysis (PD) in renal replacement therapy (RRT) remains unclear. There are no controlled trials to provide hard evidence of its efficacy. Comparative studies with haemodialysis from different centres and countries have given conflicting results even when allowing for case mix. Data from the United States on patients starting or receiving treatment in the late 1980s suggested a worse prognosis for older patients, particularly diabetics receiving PD as compared to HD. Analysis of the USRDS data base for patients starting in the early 1990s shows an improvement in outcome but with no difference in overall mortality. The Canadian registry has recently published data showing a better survival with PD than with HD in the first two years of RRT. Morbidity is similar with both therapies, although hospitalization is increased with PD. Unfortunately long-term technique survival is not as good with PD. However, PD has certain medical advantages, particularly the maintenance of residual renal function that contributes to solute and fluid removal. It may also postpone the onset of amyloidosis. Patients transplanted after previous PD have a decreased risk of early acute renal failure and equally good long-term results when compared to those patients who were on HD before transplantation. The quality of life is as good with PD as with center HD, and there are social advantages to PD including an increased chance of employment, more flexible holidays and avoidance of thrice weekly travel to a dialysis center. PD also has logistical advantages and can be utilized by the majority of new patients. We therefore conclude that PD has potential advantages early in the course of RRT, and should therefore be offered as a first option to all suitable new patients. Whether PD has a major or minor role in later years (> 5) remains unclear.     

Renal insufficiency after heart transplantation: a case-control study

BACKGROUND: In Rotterdam 304 heart transplants have been performed since 1984. End-stage renal failure, necessitating renal replacement therapy, has developed in 24 patients (8%) after an interval of 25-121 months (median 79 months). After starting renal replacement therapy one-year survival was only 60%. Overall survival after heart transplantation, however, was favourable: 5 and 10 year survival rates of 79% and 50% respectively. METHODS: A case-control study was performed to identify possible risk factors in cases who went on to develop end-stage renal failure compared to controls. RESULTS: We found that renal failure was not limited to elderly patients with ischaemic heart disease, but also occurred in young patients having dilated cardiomyopathy. A significant rise in the serum creatinine was found in cases compared to controls as early as 3 months after transplantation. Cyclosporin dose and trough levels were not different between cases and controls. Neither were there differences in the use of calcium-antagonists or other antihypertensive drugs, allopurinol or diuretics. Rejection incidence was also similar between the two groups. CONCLUSIONS: Renal failure after heart transplantation is a long term complication of cyclosporin use that is not limited to elderly patients with ischaemic heart disease. Cyclosporin dose and trough levels in the cases were not different from patients maintaining stable good renal function, indicating that cyclosporin nephrotoxicity is the result of an individually determined susceptibility to cyclosporin. Suggestions for future strategies to prevent renal failure are given.     

Successful induction and consolidation therapy of acute myeloid leukaemia in a renal allograft recipient

Immunosuppressed organ transplant recipients have a markedly increased risk of neoplasia. Among these malignancies acute myeloid leukaemia (AML) is rare. However, until now no case of successful chemotherapy has been reported. We present a 39-year-old male patient who developed AML (FAB M4 Eo) 4 years after renal transplantation and achieved a stable complete remission after induction therapy with standard dose cytarabine and daunorubicin. Remission duration is now 11 months. At present the transplant is functioning well after two additional courses of consolidation chemotherapy with high-dose cytarabine combined with mitoxantrone and idarubicine respectively. Cyclosporin A was given during all cycles of chemotherapy. We conclude that intensive chemotherapy in patients with AML following renal transplantation in good performance status is feasible.