Potassium-lowering effect of albuterol for hyperkalemia in renal failure.

To study the effect of specific beta 2-adrenergic stimulation on potassium metabolism in renal failure, we intravenously administered albuterol (Salbutamol) sulfate, 0.5 mg, to 20 patients with chronic renal failure (glomerular filtration rate, less than 5 mL/min) receiving maintenance hemodialysis. Within 30 minutes after albuterol administration, serum potassium level dropped from 5.6 +/- 0.2 (+/- SEM) to 4.5 +/- 0.2 mEq/L (5.6 +/- 0.2 to 4.5 +/- 0.2 mmol/L). There were no changes in plasma aldosterone levels or arterial pH, but blood glucose and serum insulin levels increased. Albuterol, however, induced similar decreases in serum potassium levels in three diabetic patients while free C peptide levels remained undetectable or subnormal after administration of the drug. Albuterol sulfate alone (0.5 mg intravenously) was also used to treat 24 patients with acute or chronic renal failure and hyperkalemia. Their serum potassium levels dropped from 7 +/- 0.2 mEq/L (7 +/- 0.2 mmol/L) to 5.6 +/- 0.2 mEq/L (5.6 +/- 0.2 mmol/L), 5.6 +/- 0.2 mEq/L (5.6 +/- 0.2 mmol/L), 6 +/- 0.2 mEq/L (6 +/- 0.2 mmol/L), and 6.2 +/- 0.2 mEq/L (6.2 +/- 0.2 mmol/L) at 30, 60, 180, and 360 minutes after receiving albuterol, respectively, and this was accompanied by reversal of the electrocardiographic manifestations of hyperkalemia. Despite inducing transient tachycardia, albuterol was remarkably well tolerated and no serious side effects were observed. beta 2-adrenergic stimulation of intracellular potassium uptake by albuterol is a safe and effective alternative for the treatment of hyperkalemia in renal failure.

Familial IgA nephropathy: report of two cases and brief review of the literature.

Immunoglobulin A nephropathy developed in two siblings who shared the DRw4 antigen but who were otherwise HLA-A, -B, and -C unrelated. It is suggested that a genetically induced alteration in the immune response can cause some of the cases of mesangial IgA glomerulopathy and that close blood reltaives of patients with this disease should be checked for the possible existence of renal abnormalities.

Electron-dense deposits in the renal arterioles of two patients with hypersensitivity vasculitis.

Immune complex deposition in the vessel wall is presumed to be the major pathogenetic mechanism leading to hypersensitivity vasculitis. Despite this, histologic evidence of vascular immune complex deposition such as that provided by electron-dense deposits has been reported only rarely in dermal vessels and never in visceral organs. The cases of two patients with hypersensitivity vasculitis affecting primarily the skin and the kidney are reported. Clinical renal involvement was manifested by proteinuria, hematuria, and a moderate increase in serum creatinine in one case. Renal biopsy showed minimal glomerular changes in one patient and focal necrotizing glomerulitis in the other. The arterioles appeared normal on light microscopic examination. However, obvious electron-dense deposits in the arteriolar wall could be demonstrated electron microscopically in both cases. This observation lends strong support to the theory of immune-complex-mediated vascular damage as the main pathophysiologic mechanism in vasculitis with visceral involvement.

Acute and rapidly progressive forms of glomerulonephritis in the elderly.

This article presents a comparison of acute glomerular nephritis (AGN) with rapidly progressive glomerular nephritis (RPGN) in patients aged 60 or older. In 7 elderly patients with AGN, the renal disease was preceded by skin infection (4 cases), sore throat (2 cases), or pneumonia (1 case). The 7 patients with RPGN had no history of prior infection. Both AGN and RPGN were manifested clinically as acute renal failure, but the RPGN patients had significantly higher serum creatinine levels and lower hematocrit readings. Hypocomplementemia was a feature only of AGN. The biopsy specimens from patients with RPGN showed crescents in 50--100 percent of the glomeruli, whereas specimens from patients with AGN showed no significant extracapillary proliferation. Six AGN patients recovered and 1 died. Despite dialysis, 4 RPGN patients died and the remaining 3 require maintenance dialysis. It is concluded that AGN in the elderly is more common than previously believed, frequently follows skin infections, and has a reasonably good prognosis. In contrast, RPGN, also not rare in the elderly, has a much worse prognosis.

Effect of antihypertensive treatment on the increased beta 2-adrenoceptor density in patients with essential hypertension.

The effect of different antihypertensive drugs on the increased surface beta 2-adrenoceptor density in essential hypertension was evaluated to elucidate whether the possible effect of the treatment on these receptors was secondary to blood pressure decreases or a specific effect of the drugs. Thirty-nine untreated essential hypertensive patients and 28 normotensive control subjects were studied in basal conditions. Hypertensive patients were randomly assigned to three treatment groups: bisoprolol (10 mg/day, n = 15), enalapril (20 mg/day, n = 12), and verapamil SR (240 mg/day, n = 12), and were studied before and after 1 month of treatment. Plasma catecholamines were determined by a radioenzymatic assay. Surface beta 2-adrenoceptors were measured in intact lymphocytes by radioligand binding assay using the hydrophilic ligand [3H]-CGP12177. beta 2-adrenoceptor density was increased in hypertensive patients (P < .01). After treatment, mean blood pressure decreased similarly in the three groups, while plasma catecholamines showed no significant changes in any group. beta 2-adrenoceptor number decreased only in bisoprolol-treated patients (P < .05). Mean blood pressure decreases correlated with beta 2-adrenoceptor decrements only in bisoprolol-treated patients (r = 0.65, P < .05). beta 2-adrenoceptor density correlated with plasma epinephrine levels in the control group (r = -0.50, P < .01), but not in hypertensive patients before treatment. This correlation was also observed in hypertensive patients treated with bisoprolol (r = -0.52, P < .05), but not in those treated with verapamil or enalapril. Our results suggest that bisoprolol treatment reduces the increased surface beta 2-adrenoceptor density and restores its regulation by epinephrine in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen gene M235T and T174M polymorphisms in essential hypertension: relation with target organ damage.

The molecular variants M235T and T174M of the angiotensinogen gene have been linked to essential hypertension in some populations, but there are discrepancies about this association in other studies. We studied 75 patients with essential hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years, 30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a family history of the disease. Target organ damage was evaluated by measuring urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family history of cardiovascular disease were selected. M235T and T174M angiotensinogen genotypes were determined by PCR and subsequent digestion of the products with SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28, not significantly different (P = .93) from that of the controls (MM 0.28, MT 0.44, and TT 0.28). For the variant T174M, the genotype frequencies in hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02). Similarly, there was no evidence for association between angiotensinogen genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with severe (stage III) hypertension (n = 31). Within the group of patients with essential hypertension, there were no differences in genotype distribution between patients with and without retinopathy (n = 31), left ventricular hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T and T174M variants are not associated either with essential hypertension or with target organ damage in a Spanish sample.

Platelet activation on hemodialysis: influence of dialysis membranes.

During hemodialysis, platelets are activated and release alpha-granule-specific proteins. GMP-140 is a glycoprotein stored in the alpha-granules of platelets, which is selectively expressed on the plasma membrane of activated platelets. Using a specific monoclonal antibody against this protein (CD 62), we have evaluated the influence of different dialysis membranes on hemodialysis-induced platelet activation in vivo by flow cytometry in nine patients with end-stage renal disease on maintenance hemodialysis. Five membranes were evaluated: Cuprophane, cellulose acetate, polymethylmethacrylate, polysulphone and polyacrylonitrile (AN-69). Blood samples were obtained before hemodialysis and from the inlet and outlet lines five minutes after the beginning of hemodialysis. A significant increase in the GMP-140 expression was observed in samples obtained from the outlet line compared with samples obtained from the inlet line for all membranes evaluated, but the extent of this increase depended on the type of membrane used: Cuprophane 13.95 +/- 3.94%, cellulose acetate 7.4 +/- 4.52%, polymethylmethacrylate 6.93 +/- 4.6%, polysulphone 3.83 +/- 2%, and AN-69 2.14 +/- 2.19% (mean +/- SD). Cuprophane induced the highest degree of platelet activation (P < 0.05). Cellulose acetate and polymethylmethacrylate induced more platelet activation than polysulphone or AN-69 (P < 0.05). These data demonstrate that all hemodialysis membranes induce platelet activation but to a variable extent, cuprophane being the most activating membrane, cellulose acetate and polymethylmethacrylate showing an intermediate potential of activation, while the more biocompatible membranes, polysulphone and AN-69, inducing the lowest degree of platelet activation.

Extracorporeal renal surgery. Work bench surgery.

In cases in which renal repair through conventional in situ surgery is not possible, we have proceeded to remove the organ outside of the human body and placed in on a work bench where exsitu repair is aided by microsurgery, x-ray films, and image amplifiers. In most cases the damaged kidney has recovered its function and a grave problem has been solved. Extracorporeal surgery means a new tactical solution to extreme situations.

Effect of antihypertensive treatment on intracellular calcium concentration and intracellular pH in essential hypertension.

The platelet intracellular calcium concentration ([Ca2+]i) and intracellular pH (pHi) were measured by spectrofluorimetry with the dyes Fura-2 and BCECF, respectively, in 19 patients with essential hypertension (10 males), aged 48 +/- 2 years, before and after 12 weeks of antihypertensive treatment and in 19 normotensive controls (11 males), aged 46 +/- 3 years. [Ca2+]i and pHi were measured in the resting state and after stimulation in vitro with 0.1 U/ml human thrombin. In patients with essential hypertension, both resting [Ca2+]i (61 +/- 4 nmol/l) and thrombin-induced maximal increase in [Ca2]i (291 +/- 26 nmol/l) were significantly (P < 0.01) greater than in the normotensive controls (resting 49 +/- 2 nmol/l and thrombin-induced 199 +/- 21 nmol/l). With respect to pHi, no difference in resting pHi between both groups was found (7.16 +/- 0.01 vs. 7.16 +/- 0.01). However, pHi increment at 300 seconds in response to thrombin was higher in the patients with essential hypertension than in the controls (0.131 +/- 0.02 vs. 0.083 +/- 0.01 pH units, P < 0.05). The increment in pHi was blunted by the amiloride derivative EIPA, indicating that it was mediated by the Na+/H+ exchanger. After antihypertensive therapy in the essential hypertensive patients, basal [Ca2+]i was significantly reduced (52 +/- 2 nmol/l, P < 0.01) and was not statistically different to the value found in the normotensive controls. Resting pHi suffered no significant modification after treatment (7.17 +/- 0.01, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor markers in patients with chronic renal failure.

In order to evaluate the specificity of tumor markers in chronic renal failure, we have determined serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), carbohydrate antigen 50 (CA 50), alphafetoprotein (AFP), neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), squamous cell carcinoma antigen (SCC), carbohydrate antigen 15.3 (CA 15.3) and carbohydrate antigen 125 (CA 125) in 30 patients with chronic renal failure and in 36 hemodialyzed patients without clinical evidence of neoplasia. CEA, CA 50, NSE and SCC frequently show increased serum levels, suggesting a renal metabolism, while others remain, generally, within the normal levels.

Pathological fractures in patients who have amyloidosis associated with dialysis. A report of five cases.

We are reporting the cases of five patients in whom a pathological fracture of the femoral neck developed secondary to massive deposition of amyloid while they were receiving maintenance hemodialysis. The immunohistochemical studies demonstrated the presence of beta-2-microglobulin as the major constituent protein of the amyloid deposits.

Pseudoprimary aldosteronism from the topical application of 9-alpha-fluorprednisolone to the skin.

A 56 year old man presented with hypertension, hypokalemia and depressed plasma renin activity. Plasma aldosterone was normal, but was considered inappropriate in the presence of hypokalemia. An adrenal scan showed unilateral uptake of 131I-cholesterol and a presumptive diagnosis of adrenal adenoma was made. At surgery, no adenoma was found. Instead, the adrenal was atrophic, and in this case also contained caseating granulomas. Postoperative plasma aldosterone values were consistently normal and adrenocortical insufficiency was ruled out. On requestioning, the patient admitted long-term topical use of a skin cream containing 9-alpha-fluorprednisolone. Withdrawal of the fluorprednisolone cream led to normalization of blood pressure and serum potassium, and on renewed contact with the drug, hypertension and hypokalemia reappeared. The patient is now normotensive and normokalemic after permanent discontinuation of the cream. Topical cutaneous application of 9-alpha-fluorprednisolone can induce a syndrome closely mimicking primary aldosteronism. A high degree of suspicion and adequate history taking are critical for the appropriate management of such patients and the avoidance of unnecessary or dangerous procedures.

Renin-induced massive proteinuria in man.

A 30 year old man developed renovascular hypertension and extreme elevation of plasma renin activity. Daily proteinuria ranged from 13 to 31 g. There were no criteria for the diagnosis of malignant hypertension. A primary glomerulopathy was excluded by a basically normal renal biopsy from the unprotected kidney. On electron microscopy the epithelial cell foot processes were not fused, thus ruling out simultaneous lipoid nephrosis. The source of renin was removed by means of a left nephrectomy. Following the procedure the patient became normotensive, the renin values normalized and the proteinuria disappeared. The results suggest that renin can cause significant proteinuria in man.

Malignant or accelerated hypertension in IgA nephropathy.

A retrospective analysis of 66 adult patients diagnosed as having IgA nephropathy by renal biopsy revealed that 24 (36%) were hypertensive when first seen. Of these hypertensive patients, 10 (15%) had malignant or accelerated hypertension. All patients but one were male and had no knowledge of their renal disease and sought medical advice for symptoms due to hypertension. Five patients had no history of gross hematuria. Histological vascular findings showed, in three proliferative endarteritis and fibrinoid necrosis, in five arteriolosclerosis and in two vascular hypertrophy. In spite of good blood pressure control, six patients reached terminal uremia within a maximum of 14 months. In summary, the incidence of malignant hypertension in adults with IgA nephropathy is higher than previously reported, and its true incidence can only be known if more histopathologic studies of patients with malignant hypertension are performed. Patients with this association reach end stage renal failure in a short period of time.

Long-term evolution of patients with isolated C3 mesangial glomerulonephritis.

Isolated mesangial C3 proliferative glomerulonephritis is a nephropathy poorly defined among glomerular diseases. Clinical picture is characterized by episodes of gross hematuria and/or persistent or recurrent microhematuria and/or proteinuria. Short-term prognosis (less than 3 years) is considered to be benign, although not much information is available in reference to long-term follow-up. We reviewed all renal biopsies performed in our center between 1978 and 1992 (n = 2,200) in order to study clinical course of these patients. Isolated mesangial C3 deposition was found in 11 cases (0.5%). Isolated proteinuria (> 0.5 g/d) was present in 3 patients and nephrotic syndrome in 2. Hematuria with proteinuria was detected in 5 patients. In one patient hematuria was the only clinical finding. Arterial hypertension was observed in 4 cases. At the time of renal biopsy, renal function was accurately normal in all but one patient. In our series, renal function showed no changes during the first 3 years, accordingly to data referred to in the literature. After 7 years of follow-up, however, renal function was declining in 4 of 5 patients who developed terminal renal failure up to requiring hemodialysis. Therefore, initial benign prognosis ascribed to this glomerulonephritis would not be confirmed in a long-term follow-up.

Cytomegalovirus colitis in chronic renal failure.

Cytomegalovirus (CMV) is an ubiquitous agent and is recognized as a pathogen in all age groups. Although symptomatic infection by CMV (CMV disease) in normal adults is generally mild, the virus is known to produce severe symptoms, mostly in immunocompromised patients. In this group of patients, the primary involvement of the colon by CMV is reported to be rare. However, chronic renal failure patients are prone to CMV infection. Nevertheless, despite the high incidence of infection in these patients and the recognition of a defective immune response in some of them, clinical manifestations are an exception. Two chronic renal failure patients who developed acute colitis due to CMV infection are presented. Of interest are the rarity of the association, the favorable clinical course and the differential diagnosis with other gastrointestinal disorders which are more common in these patients.

Silent renal disease in systemic lupus erythematosus.

Several recent studies have focused on the discrepancy between lupus nephropathy and clinical renal involvement and, consequently, question the relevance of renal biopsy in these patients. We analyze the clinical characteristics, histological renal findings and subsequent course of patients with silent renal disease. Renal biopsy was performed in 15 patients with systemic lupus erythematosus (SLE) who had no clinical signs of renal involvement (no urinary sediment abnormalities, absence of proteinuria and serum creatinine less than 1.3 mg/dl). All biopsies were classified according to a modified classification proposed by the WHO. Six cases (40%) showed no histological or immunofluorescence changes (type I), 7 (47%) had mesangial nephropathy (3 type IIa and 4 type IIb) and 2 (13%) had focal proliferative glomerulonephritis (type III). None of the patients had previous evidence of neurological abnormalities. Patients with type I only had arthritis, skin lesions and Raynaud's phenomenon. By contrast, 7 patients with histological renal involvement had serositis or hemolytic anemia. All cases with silent nephropathy were treated with steroids and showed a benign clinical course with stable renal function and absence of urinary abnormalities during follow-up. We concluded that in the absence of clinical renal abnormalities, renal involvement is not uncommon in SLE. We believe that a renal biopsy should be performed mainly in those SLE patients presenting with clinical manifestations other than arthritis or cutaneous lesions since this policy may allow detection of significant silent renal injury.

Acquired renal cystic disease in HD: a study of 82 nephrectomies in young patients.

In order to study the development of acquired renal cystic disease (ARCD) and its potential complications, we studied, macro- and microscopically, 82 surgical specimens of nephrectomy carried out on young patients with chronic renal failure previous to renal transplantation. Statistical correlation of pathological findings with age, sex and time on hemodialysis (HD) have been done. There were 72 cases of ARCD (87.8%). It was statistically correlated with male sex (p less than 0.02) and prolonged time on HD (p less than 0.001) as has been previously reported. Hyperplasia of the cystic epithelium was found in 42 cases (52%), with 18 (22%) showing marked papillary proliferation. Also, there were 22 cases (27%) with renal adenomas. This incidence of hyperplastic and neoplastic proliferations, more than would be common in such a young population (males: 33.5 +/- 9.3 years; females: 35.4 +/- 11.7 years), suggests the potential of patients affected by ARCD to develop neoplasms. Thus, we consider that these patients must be checked periodically to detect possible malignant neoplasms.

Prognostic implication of anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) were detected in 12 out of 37 (32%) serum samples from patients with anti-glomerular basement membrane (GMB) disease by an indirect immunofluorescence assay. In 11 cases, ANCA were directed against myeloperoxidase, as revealed employing neutrophils devoid of this enzyme as the test substrate. Patients having both ANCA and anti-GBM antibodies (AGBMA) were considerably older (mean age 59 years) than patients with AGBMA alone (mean age 33 years). In addition, patients with both antibodies had some clinical and pathologic data that suggested an associated systemic vasculitis. This was supported by the fact that among these patients, those with highest ANCA titres recovered renal function despite being initially on hemodialysis, as opposed to those with lowest ANCA titres or AGBMA alone. In patients with both antibodies, there was an inverse relationship between AGBMA and ANCA values (p = 0.02). Moreover, the mean AGBMA level tended to be higher for patients with AGBMA alone than for those with both ANCA and AGBMA. These results suggest that, at least in some cases, there may be a contribution of an ANCA-related mechanism in the pathogenesis of anti-GBM disease. Although the exact role of ANCA in this and other diseases remains to be clarified, there is important clinical evidence that in anti-GBM disease ANCA may represent a serologic marker of good prognosis identifying a subset of patients who may recover renal function.

Acute visual and auditory neurotoxicity in patients with end-stage renal disease receiving desferrioxamine.

We report 5 cases of acute visual and auditory neurotoxicity in patients with end-stage renal disease receiving desferrioxamine. Four patients complained of visual toxicity characterized by a decrease in visual acuity, loss of color vision and night blindness. In these patients there was a decrease in visual acuity, and the Farnsworth's test revealed a tritanopy (yellow-blue axis impairment); 1 patient also showed retinal pigmentary changes. A fifth patient complained of bilateral and severe neurosensorial deafness. Patients improved clinically upon drug-withdrawal. We recommend careful monitoring of audiovisual toxicity in patients with end-stage renal disease receiving this drug.