Monoclonal IgE with renal failure

Only four cases of immunoglobulin E (IgE) monoclonal "gammapathies" have been reported previously. Discussed here is a 57 year old man who presented with hypertension and the nephrotic syndrome. A monoclonal IgE-kappa component (0.6 mg/ml), which did not appear as an M spike on protein electrophoresis, was demonstrated by immunoelectrophoresis in the serum and urine. The patient's condition deteriorated rapidly due to renal failure, and he died five weeks after the diagnosis was made. Pathologic examination disclosed extensive glomerular lesions, but amyloid was not detected by light or electron microscopy. The possible relationship between the monoclonal gammapathy and kidney impairment is discussed.     

Disseminated xanthosiderohistiocytosis with cardiac involvement and monoclonal gammapathy

Xanthosiderohistiocytosis is a rare non-Langerhans histiocytosis (4 reported cases). The clinical characteristics include diffuse, sometimes deep, dark-brown infiltrations of the skin. Histological examination reveals abundant deposits of haemosiderin within the histiocyte proliferation. This entity is a clinical form of Montgomery's disease (xanthoma disseminatum) which has been reported in over 100 cases. Our case of disseminated xanthosiderohistiocytosis was particular because it involved the heart and was associated with a monoclonal gammapathy. Five cases have been reported associating xanthoma disseminatum and monoclonal gammapathy, including one case of xanthosiderohistiocytosis. In our case, rapidly increasing levels of monoclonal immunoglobulin suggested an evolution towards a myeloma. A monoclonal gammapathy should be looked for and monitored in cases of xanthosiderohistiocytosis, and more generally xanthoma disseminatum because of the risk of developing lymphoma or myeloma.     

Hepatic failure in a case of multiple myeloma-associated amyloidosis (kappa-AL)

We report a case of kappa-AL amyloidosis which rapidly developed hepatic failure in a 79-year-old Japanese female who was admitted to our hospital because of abdominal distension and loss of appetite. Laboratory examination revealed a marked deterioration of liver function with cholestasis and monoclonal gammapathy. At the time that the diagnosis of IgG-kappa type multiple myeloma was made, jaundice was advanced, with continuous gastrointestinal bleeding. The patient died of hepatic failure 2 weeks after admission. Needle biopsy of the liver revealed a diffuse, massive deposition of amyloid protein.     

N-acetyl-beta-glucosaminidase, beta-glucuronidase and beta-galactosidase in the leukocytes, serum and urine of healthy subjects and patients with immunocytoma

The activity of GlcNAc-ase, GlcUA-ase and Gal-ase was determined in the leukocytes serum and urine of 23 patients with M. M., 11 patients with other neoplasms including 9 with lymphoreticular proliferative processes without associated monoclonal gammapathy. The range of normal enzyme activity was established in the investigations carried out in 45 health subjects. In the group of patients with M. M. without complications. normal activity of GlcNAc-ase, GlcUA-ase and Gal-ase was found in the leukocytes. In the group of patients with white blood cell count below 2.5 g/l and in cases after long-term treatment with Alkeran the activity of GlcNAc-ase and GlcUA-ase in the leukocytes was reduced. In the patients with M. M. the activity of GlcNAc-ase was raised in the serum and urine, and this activity was higher in cases with longer duration of the disease and more advanced pathological process. The patients with M-IgG protein showed a higher GlcNAc-ase activity in the serum and urine than those with protein M-IgA. A higher activity of GlcNAc-ase in the serum and urine than those with protein M-IgGK than in those with M-IgG gamma. In patients with M. M with renal complications the urinary activity of GlcNAc-ase was higher than in patients with M. M. without renal complications. In CLL the activity of GlcNAc-ase was found to be decreased in the leukocytes and raised in the urine. In patients with Hodgkin's disease the activity of the studied enzymes was raised in leukocytes while the results of their determinations in serum and urine were equivocal.     

Hypertension in autosomal dominant polycystic kidney disease

Hypertension occurs frequently in autosomal dominant polycystic kidney disease. Increased activity of the renin-angiotensin system contributes to the development and maintenance of hypertension before the development of renal failure. Angiotensin-converting enzyme inhibitors are indicated for treatment of hypertension before the development of renal failure, but in severe renal failure these agents may cause further deterioration in renal function. Treatment of hypertension may not retard the progression of renal failure but is necessary for the prevention of cardiovascular disease.     

Fitting a hand-glove prosthesis to enhance the reconstructed mutilated hand

We report a unique case of tubular polyclonal immunoglobulin G (IgG) deposition disease (PIDD) superimposed on diabetic nephropathy in an 84-year-old man presenting with subacute renal failure and proteinuria. The deposits were located exclusively between the tubular epithelial cells and the tubular basement membranes (TBMs) and stained intensely with antisera to IgG heavy chain and both kappa and lambda light chains. Electron microscopy revealed large predominantly extracellular electron-dense deposits with a distinctive curvilinear substructure. The associated light microscopic findings of tubular simplification with features of acute tubular necrosis implicate this tubulopathy as the cause of the acute renal failure. This appears to represent a unique entity that does not fit into any previously described category of renal tubular immune complex or immunoglobulin deposition disease.     

Autoimmune interstitial nephritis and hepatitis in polyglandular autoimmune syndrome

A 6-year-old female with polyglandular autoimmune syndrome type I, chronic active hepatitis, and renal failure is described. The renal biopsy demonstrated advanced tubulointerstitial disease with antibodies directed against tubular basement membranes. The patient's serum contained circulating antibodies directed against both renal and hepatic parenchyma. Renal disease culminating in renal failure and anti-tubular basement membrane disease have not been previously reported in association with polyglandular autoimmune disease. We describe for the first time a patient with polyglandular autoimmune syndrome, chronic active hepatitis, circulating antibodies directed against both renal and hepatic parenchyma, and primary tubulointerstitial disease culminating in renal failure.     

Treatment of acute renal failure

Acute renal failure is a life threatening illness whose mortality has remained high since the introduction of hemodialysis 25 years ago, despite advances in supportive care. Acute renal failure is an extremely morbid and costly disorder with a significant proportion of patients progressing to end-stage renal disease requiring dialysis. To the nephrologist, acute renal failure remains an extremely frustrating disease, because the pathophysiology is not well understood and the limited therapeutic options force the nephrologist to sit on the sidelines and wait for renal function to return. For example, dialysis remains the only FDA-approved treatment for acute renal failure, but dialysis may also cause renal injury that prolongs renal failure. The purpose of this perspective is to understand the results of the recent, largely negative, clinical trials in view of recent advances in the epidemiology of ARF. This review will also discuss diagnostic tools, strategies for improved design of clinical trials, and other therapeutic interventions that will be needed to properly treat acute renal failure in the 21st century.     

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.     

Acute renal failure due to severe Landry-Guillain-Barré syndrome

BACKGROUND: Blood urea nitrogen (BUN) >60 mg/dl has been reported to occur commonly in patient's with severe Landry-Guillain-Barré syndrome. AIMS: To find out the cause for this high BUN we compared the renal function tests of 30 consecutive cases with severe Landry-Guillain-Barré syndrome to those of 30 controls. RESULTS: Acute renal failure occurred in seven patients with Landry-Guillain-Barré syndrome and none of the control group. Acute renal failure was found more in cases with Landry-Guillain-Barré syndrome compared to controls (P=0.0049). Six out of seven cases with Landry-Guillain-Barré syndrome and acute renal failure had dysautonomia and became oliguric while being in a hypotensive state. Of 30 patients with Landry-Guillain-Barré syndrome seven cases died. From eight patients with dysautonomia six cases who had acute renal failure died. The mortality rate was higher in cases with dysautonomia and acute renal failure (P = 0.0001 and 0.00001, respectively). Interestingly no glomerular disease was found. CONCLUSION: In conclusion acute renal failure can occur commonly in cases with severe Landry-Guillain-Barré syndrome particularly in those with dysautonomia, causing high mortality.     

Diabetes mortality in Singapore, 1991--a preliminary study

OBJECTIVES: The study was undertaken to estimate the contribution of diabetes mellitus to total mortality in Singapore and to study the mortality experience among known diabetics in Singapore by sex, age-group and ethnic group. METHODS: Death certificates of all persons who died in Singapore between 1 January 1991 and 31 August 1991 (n = 9,197) were reviewed. Records which mentioned diabetes mellitus as an underlying or contributory cause of death were selected as being a diabetic case (n = 1,010). RESULTS: If all diabetes related deaths were considered, diabetes mellitus would account for 9.3% of all deaths in Singapore in 1991, i.e. four times higher than the figure of 2.3% in the official statistics. Ischaemic heart disease was the leading cause of death in all age-groups. Renal failure was a major cause of death before the age of 55 while cerebrovascular disease and respiratory tract infections were important causes of death after the age of 64. Renal failure was the leading cause of death among Chinese diabetics below the age of 65. Ischaemic heart disease was the main cause of death among Indian and Malay diabetics. As compared to the general population, Chinese diabetics were more likely to die from renal failure while Indian and Malay diabetics were more likely to die from ischaemic heart disease.     

Fenoldopam: a new dopamine agonist for the treatment of hypertensive urgencies and emergencies

Vascular nephropathies are a steadily increasing cause of end-stage renal failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features in the hypertensive patient. This is especially true for blacks of African descent, in whom hypertension and nephrovasculopathies are a major cause of renal insufficiency. That primary hypertension leads to renal vascular lesions, glomerular obsolescence and interstitial fibrosis has long been established. It should not, however, obscure the fact that renal vascular lesions can be observed in animal models as well as in some humans, especially young blacks, in the absence of, or anticipating the onset of hypertension. This leads to considering the hypothesis that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed and that this defect is strongly associated with the hypertensive trait. Atherosclerotic renal disease is a major, potentially treatable cause of chronic renal disease is a major, potentially treatable cause of chronic renal failure, especially in whites. It leads to renal atrophy, but the ischemic kidney retains a vigorous potential for tubular cell regeneration, which pleads for early recognition and treatment. Recent data suggest that renal ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism, ranks among the multiple causes of secondary focal segmental glomerulosclerosis. Irrespective of its initial mechanism, ischemia induces renal fibrosis, the pathophysiology of which is centered on increased generation of angiotensin II. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension, and the relationship between these lesions and the unfavorable prognosis of glomerulopathies, especially primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum of nephrovasculopathies opens perspectives for investigating, understanding and treating a major mechanism of progressive renal insufficiency.     

Nephrosclerosis: current status

Nephrosclerosis is the most typical and widespread renal manifestation of hypertension and can be judged as the pathological hallmark of essential hypertension. Nephrosclerosis is an important and frequent cause of progressive renal disease, however, information in the literature on the risk of developing renal failure in the course of essential hypertension is sparse. Traditionally, nephrosclerosis was thought to result from glomerular ischemia. Alternatively, glomerular sclerosis in hypertension may result from glomerular hyperperfusion or hypertension. Studies in experimental models of renal disease have identified a promising intervention with either Ca antagonists or angiotensin-converting enzyme inhibitors. Application of these therapies to patients with nephrosclerosis should await the results of careful clinical trials.     

Acute renal failure syndromes in human immunodeficiency virus infection

Two major groups of renal complications in human immunodeficiency virus (HIV) disease are a spectrum of disorders that result in potentially reversible acute renal failure, primarily acute tubular necrosis (ATN), and HIV-associated nephropathy (HIVAN), predominantly focal and segmental glomerulosclerosis (FSGS), leading to end-stage renal disease (ESRD). Fluid-electrolyte and acid-base derangements frequently encountered in acquired immune deficiency syndrome (AIDS) are major risk factors for the development of acute renal failure (ARF). HIVAN is an unusual form of poorly responsive glomerular disease characterized by nephrotic syndrome, FSGS, and a rapid fulminant progression to ESRD. ARF syndromes encountered in HIV patients are diverse in nature; many are similar to that in non-HIV subjects, whereas some are more common and unique. In general, HIV disease patients with ARF are younger and much sicker. Although ATN secondary to ischemic and toxic injuries is the commonest ARF syndrome, urinary obstruction is a rare cause of severe renal failure. In many AIDS patients afflicted with complicated infections and multi-organ failure, ATN is a terminal event, whereas in others treated aggressively, ARF is associated with good prognosis. In our large comparative study of severe ARF, recovery of renal function and mortality were determined by patient's general hemodynamic status, and not by the presence or absence of HIV infection. The prognosis of hemolytic uremic and thrombotic thrombocytopenic purpura syndromes often observed in HIV patients is much worse than in non-HIV patients. The syndrome of crystalluria-induced ARF is common, and protease inhibitor induced disease is confined to HIV patients.     

Current therapy of chronic renal failure

The course of chronic renal failure is generally progressive and mediated by several factors that operate in combination. Several extrarenal events which may cause transient or permanent deterioration of renal function, are important, because their correction may slow the progression of renal disease e.g. volume disorders, infection, nephrotoxic agents. In progression of chronic renal disease leading factors are hypertension, proteinuria and high protein/phosphorus intake. Number of evidence suggests that ameliorating hypertension, reducing proteinuria slow the progression of chronic renal failure. Clinical studies in diabetic nephropathy demonstrated that the renoprotective effect of ACE inhibitors was independent of their effect of systemic blood pressure. In ESRD patients access for renal replacement therapy should be obtained as early as possible. An A-V fistula may take several weeks to mature especially in diabetic or elderly patients. Early dialysis has been advocated in diabetic patients. In general, patients can start ESRD therapy when residual kidney function drops to 5-10% of normal value. High quality of dialysis should be provided to the uremic patient with respect of successful renal transplantation.     

Metabolic encephalopathy as a complication of renal failure: mechanisms and mediators

Among patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may develop symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and progressive intellectual dysfunction. Peripheral neuropathy is also a major cause of disability in uremic subjects. It is believed that aluminum contributes to the pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in patients with renal failure, probably because of actions of parathyroid hormone on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual dysfunction, dialysis dementia, and uremic neuropathy can be made by the characteristic clinical pictures of these syndromes and the exclusion of other causes of nervous system dysfunction.     

Prevalence of diabetic nephropathy in adult patients with chronic kidney failure

Diabetic nephropathy is a frequent cause of end-stage renal failure in patients admitted for renal replacement therapy. PURPOSE: To evaluate the prevalence of DN, as the underline disease, in patients with ESRF. METHODS: 1,303 [male (M) = 767 and female (F) = 536] patients with ESRF who were on a waiting list for cadaver kidney transplant at Nephrology Unit-University Hospital (HC-UNICAMP), from August/90 to June/93--group 1--and 193 (M = 112 and F = 81) patients admitted for renal replacement therapy in a year period (April/92 to March/93), in the city of Campinas, State of S?o Paulo, Brazil, were studied. RESULTS: The prevalence of DN was 10.1% in group 1 and 17.6% in group 2 (x2 = 7.15; p = 0.007), being the third cause of ESRF in both groups, and it was preceded by glomerulonephritis and arterial hypertension. In group 1 the reduction of number of patients with increase in duration of dialysis was significantly greater in patients with diabetic nephropathy (x2 = 30.9; p < 0.001). Among patients with DN 35 (26%) in group 1 and 6 (18%) in group 2 had less than 35 years when they were admitted for renal replacement therapy and are likely to be type 1 (insulin-dependent) diabetic patients. CONCLUSION: In our studied groups DN was a frequent cause of ESRF.     

Late occurrence of cysts in autosomal dominant medullary cystic kidney disease

Medullary cystic kidney disease (MCD) is characterized by multiple renal cysts at the corticomedullary boundary area, by autosomal dominant inheritance, and by onset of chronic renal failure in the third decade of life. We report on a family with three affected individuals of both sexes in two generations presenting with end-stage renal failure at age 22-31 years. Primarily diagnoses considered included unclassified hereditary nephropathy and autosomal dominant polycystic kidney disease. Careful evaluation of all findings, initiated after investigation of renal morphology with CT, revealed features characteristic for MCD and led to the final diagnosis of MCD. We conclude that MCD is an important differential diagnosis for polycystic kidney disease in young adults with end-stage renal failure. Establishing the correct diagnosis has considerable impact for genetic counselling.     

Leukocytes, cell adhesion molecules and ischemic acute renal failure

Ischemic acute renal failure (ARF) is a common clinical syndrome, associated with high morbidity and mortality, for which there is no specific therapy. Polymorphonuclear neutrophils (PMN) recruited during reperfusion have been implicated as mediators of renal parenchymal injury in ischemic ARF. Leukocyte adhesion molecules appear to facilitate PMN recruitment in this setting. Complementary studies using monoclonal antibodies, antisense oligonucleotides and gene "knock-out" indicate that blockade of CD11/CD18 integrins and intercellular adhesion molecule-1 (ICAM-1) attenuates ARF in some experimental models of renal ischemia. These exciting observations may herald the development of novel anti-adhesion strategies for use in human disease.     

A Jordanian view about cancer knowledge and attitudes

Inherited polycystic kidney disease (PKD) in children is a disorder characterized by diffuse cystic involvement of both kidneys, without evidence of dysplasia. Both forms, autosomal recessive (ARPKD) and autosomal dominant (ADPKD) have considerable overlap in clinical presentation and radiographic features in the pediatric population. At present, a prenatal diagnosis is possible with ultrasound examination. A brief review of the literature is here reported. The knowledge of pathophysiological and clinical data is requested, since PKD represents a major cause of renal failure in pediatrics.