Renal protection and angiotensin converting enzyme inhibition in microalbuminuric type I and type II diabetic patients

BACKGROUND: Many studies have emphasized the role of antihypertensive drugs and in particular angiotension converting enzyme (ACE) inhibitors in the retardation of diabetic nephropathy. Although these studies have focused predominantly on patients with overt proteinuria, more recently a number of investigators have explored the role of ACE inhibitors in both type I and type II diabetic patients with an earlier phase of diabetic renal disease known as microalbuminuria. These agents are now being considered as renoprotective agents not only in hypertensive patients but also in those with 'normal' blood pressure. Initially, studies in type I diabetic patients showed that ACE inhibition was effective in retarding the increase in albuminuria which was observed in placebo treated groups. More recently, several multi-centre placebo controlled studies have been performed suggesting that prolonged treatment not only reduced albuminuria but also preserved renal function. The role of ACE inhibition in microalbuminuric type II diabetic patients is less well characterised although several studies have recently described beneficial effects of ACE inhibition on albuminuria and possibly on renal function. REVIEW: Although ACE inhibitors have been clearly shown to reduce urinary albumin excretion in diabetic patients, the issue as to whether they confer a specific benefit over other classes of antihypertensive agents remains controversial. Several meta-analyses have suggested that ACE inhibitors are more potent at decreasing albuminuria or proteinuria than other antihypertensive agents, for a given reduction in blood pressure. The Melbourne Diabetic Nephropathy Study Group has instituted a study which is placebo-controlled and is confined to normotensive type I and type II diabetic patients. The ACE inhibitor perindopril has been compared not only with placebo but also with the dihydropyridine calcium channel blocker, nifedipine. Preliminary analysis reveals that after 12 and 24 months of treatment, perindopril is more effective in reducing albuminuria than placebo or nifedipine. CONCLUSION: ACE inhibitors are a promising class of antihypertensive agents in diabetic patients with microalbuminuria. These drugs should be considered as first line agents in such patients, even in the absence of systemic hypertension.     

Renal function and urinary urokinase in hypertensive and diabetic pregnancies

In Vanuatu malaria is a major killer, especially of young children. As most deaths occur outside the hospital it is very important to have simple, clear guidelines on the management of patients with suspected malaria for the primary health care workers who treat the majority of cases. Despite the encouragement of early treatment, malaria was the major cause of death in children after the neonatal period in 1988. During 1989 and 1990 the treatment of malaria in Vanuatu was reviewed with the aim of trying to reduce the morbidity and mortality from the disease. New guidelines were included in the Vanuatu Health Workers' Manual, issued to all nurses, nurse practitioners and doctors in 1991. The major changes were the introduction of immediate slide microscopy, the use of a combination of chloroquine and sulphadoxine-pyrimethamine for Plasmodium falciparum malaria and for children under 5 years and pregnant women, the discontinuation of single-dose primaquine (previously given as a gametocytocidal agent), and the use of a loading dose of quinine. The constraints of the previous guidelines, the rationale for the changes and the expected improvements resulting from using the new treatments are discussed.     

Renal calculus dissolution in immobilized patients

13 patients presenting with immobilization stones are reported. Young males with an infection of the urinary tract are most commonly affected. In the case of phosphate stones, the infection of the urinary tract with an alkaline shift of the pH and an idiopathic hyperuricosuria play a decisive part together with temporary hyperphosphaturia and hypercalciuria. The importance of urea splitting bacteria in the urine for stone formation is stressed. Applied in time increase of fluid intake, specific antibiotics and allopurinol can lead to litholysis. If the urine of immobilized patients were monitored closely from the beginning of the hospitalisation for the above factors, and treated appropriately, urine calculi should be largely prevented.     

Prevention of renal osteodystrophy in peritoneal dialysis

BACKGROUND: Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in understanding the pathogenesis of secondary hyperparathyroidism (sHPT) during recent years, prevention and treatment of ROD is still suboptimal, requiring surgical parathyroidectomy in 6 to 10% of all patients on dialysis after 10 years. In addition, the spectrum of bone lesions has changed, with non-aluminum-related adynamic bone disease (ABD) found in up to 43% of peritoneal dialysis (PD) patients. METHODS: Current recommendations concerning prevention of ROD in PD based on the literature and personal recent data were reviewed. The focus is on (i) the importance of early prophylactic intervention to prevent parathyroid gland hyperplasia, (ii) the pathogenesis of ABD, and (iii) the role of metabolic acidosis in ROD. RESULTS: There is ample evidence that sHPT starts early during the course of renal failure and results from both hypersecretion of PTH by parathyroid cells and glandular hyperplasia. As shown by experimental and clinical studies, established parathyroid cell hyperplasia is hardly reversible by pharmacological means, and therefore prevention of parathyroid cell proliferation needs to start early. Recent data from randomized trials document the efficacy and safety of low dose active vitamin D (0.125 to 0.25 microgram/day) and/or an oral calcium substitute to prevent progression of sHPT in patients with mild to moderate renal failure. Since little is known about the pathogenesis, natural course and clinical impact of ABD in PD, specific therapeutic concepts have not yet been generated. Diabetes and advanced age are established risk factors, whereas the role of calcium and vitamin D overtreatment or the type of dialysis (PD vs. HD) are still controversial. Currently no evidence for different functional behavior of the parathyroids in ABD and sHPT has been found. The role of circulating or local factors such as cytokines, growth factors or the presence of advanced glycation end-product (AGE)-modified matrix proteins for the pathogenesis of either type of ROD deserves further investigation. Avoiding oversuppression of parathyroid gland and the use of low calcium dialysate may help prevent ABD. There is growing evidence that a correction of metabolic acidosis will influence ROD by both direct effects on the bone and on parathyroid cell function. New dialysate composition for CAPD with a high HCO3 concentration will allow normalization of acid-based metabolism in PD patients. Their effects on ROD under long term conditions remain to be determined. CONCLUSION: Therapeutic efforts should aim to prevent the development of parathyroid gland hyperplasia and sHPT early during the course of renal failure, and should include the use of low dose vitamin D therapy and oral calcium substitution as well as correction of metabolic acidosis. Concerning ABD, more information is needed regarding the causes and consequences of this type of bone lesion to develop a more specific therapy.     

Changes in capillary permeability in diabetic patients

Microangiopathic disorders, characterized by capillary vasodilation and increases in capillary blood flow and permeability, are common in diabetes and can occur before the development of microangiopathic complications. In a study of 163 diabetic patients, capillary permeability, measured by albumin retention (AR), was increased in 39% of patients. AR was increased more frequently in women than in men, and in patients without microangiopathic complications than in patients with complications. Increased AR was significantly associated with insulin-dependent diabetes in male patients. Lymphatic function was abnormal in 72% of patients; this abnormality was often present before AR increased. The pathophysiology of microangiopathy is complex and involves metabolic, haemodynamic, neurological and hormonal factors. Improved control of glycaemia and blood pressure can reduce capillary permeability. In addition, studies with a flavonoid fraction and n-3 polyunsaturated fatty acids suggest that these agents may also be beneficial.     

Fatal hand sepsis in Tanzanian diabetic patients

Hand infections are common presentations among diabetic patients admitted to hospital in Tanzania. The morbidity and mortality are high and patients' hospital inpatient stay tend to be prolonged because of suboptimal therapy. We describe four diabetic patients with hand infections and fatal outcomes. In contrast to patients with foot infections, none of our patients had clinical evidence of peripheral neuropathy or vascular disease. All four patients eventually died in hospital after acquiring hand sepsis and diabetic ketoacidosis which did not respond to prolonged courses of intravenous insulin and antimicrobials. Literature review suggests such infections are at least as likely to include Gram-negative organisms as Staphylococcus aureus. Primary management should have included aggressive surgery with limb amputation if necessary with adjunctive antimicrobial therapy.     

Hemorheological disorders in patients with diabetic retinopathies

Disorders of blood rheology resultant from hyperglycemia play the key role in the development of diabetic involvement of the eye. Electrical stability of red cell membranes, blood viscosity, and electrophoretic mobility of erythrocytes were studied in 72 patients with various forms of diabetes mellitus. Correlations of these parameters with the severity of retinal involvement and the form of the underlying disease were detected. Blood rheology characteristics were notably shifted in the group of patients with proliferative diabetic retinopathy, in comparison with those in controls. Disorders of the erythrocyte membrane were found in the cohort of patients examined.     

Renal failure in two patients with Wolfram syndrome

BACKGROUND/OBJECTIVE: Aluminium is produced from the mineral bauxite. Occupational exposure is reported during the industrial processing of aluminium and is associated with pulmonary and neurotoxicity. However, data on exposure and toxicity of workers in the open bauxite mining industry do not exist. Therefore, a study was performed to explore aluminium exposure in employees involved in this bauxite mining process in a Surinam mine. METHODS/DESIGN: A group of workers occupationally exposed to aluminium in an open bauxite mine were compared with a group of nonexposed wood processors. Serum aluminium was analyzed using atomic absorption spectrometry Data from the clinical chemistry of the blood and a questionnaire were used to explore determinants for aluminium exposure. RESULTS: No significant difference between serum aluminium in the exposed (4.4 +/- 2.0 micrograms/L, n = 27) and control group (5.1 +/- 1.5 micrograms/L, n = 27) was detected. For the serum concentration of the clinical chemical variables (calcium, citrate, and creatinine), a statistically significant difference was computed (p < or = 0.02) between the exposed and control group. All levels were slightly higher in the exposed group; no statistically significant correlations with serum aluminium were found. CONCLUSIONS: In this study, serum aluminium values were in the normal range, no significant difference between the groups could be detected despite long-term occupational exposure.