Physical work capacity in chronic renal disease

We studied the physical fitness of 71 patients with renal disease before dialysis, after starting dialysis, and after successful renal transplantation. Maximal muscle strength was determined in 58 patients and maximal cardiovascular capacity was assessed in 36 patients. Before dialysis there was a 31 percent reduction in muscle strength in men and 47 percent in women. The loss of muscle strength was most pronounced in the leg extensors. Cardiovascular capacity and muscle strength was positively correlated in the dialysis patients (p less than or equal to 0.05). The cardiovascular capacity was decreased 29% in predialysis patients, 45% in dialysis patients and 37% in transplanted patients compared to untrained healthy controls. The predialysis patients had a 19% greater cardiovascular capacity than the dialysis patients and a 9% greater cardiovascular capacity than the transplanted patients. While hemoglobin concentrations showed a positive correlation (p less than or equal to 0.05) with maximal cardiovascular capacity and creatinine concentration showed a negative correlation (p less than or equal to 0.05) with maximal cardiovascular capacity in the predialysis patients, hemoglobin concentrations and creatinine concentrations did not correlate with cardiovascular capacity in the dialysed and transplanted patients. In dialysis patients as well as in patients after kidney transplantation hemoglobin and creatinine concentrations, muscle strength, height, weight, and age are factors influencing the physical work capacity, but none of these variables alone seems to be a strong determination factor. Besides the complications of kidney disease which may itself reduce physical fitness, the lack of physical training is an important factor in determining the residual muscle strength and cardiovascular capacity for all patients with renal insufficiency.     

Neuropsychiatric aspects of chronic renal disease

Chronic renal disease, hemodialysis, and renal transplantation may be accompanied by a variety of derangements of higher cortical functioning, mental processes, and behavior. Many treatable toxic metabolic, degenerative, and structural processes may occur as a result of the progression of the renal disease itself, associated medical conditions, or secondary neurologic complications. Associated behavioral changes may easily be confused with functional disorders. latrogenic complications may also arise. An understanding and awareness of these entities is important for the consulting psychiatrist in order to properly diagnose and care for the renal patient who shows disturbances in behavior.     

Analgesic use and chronic renal disease

To examine the use of analgesics as a cause of chronic renal disease, we performed a multicenter case-control study of 554 adults with newly diagnosed kidney disease (serum creatinine, greater than or equal to 130 mumol per liter [1.5 mg per deciliter]) and 516 matched control subjects selected randomly from the same area of North Carolina. Histories of use of analgesics (phenacetin, acetaminophen, and aspirin) were obtained by telephone interview with the patients or their proxies. Daily users of analgesics had significantly more renal disease than infrequent users (odds ratio, 2.79; 95 percent confidence interval, 1.85 to 4.21). The risk of renal disease was highest in daily users of phenacetin (odds ratio, 5.11; confidence interval, 1.76 to 14.9, after adjustment for the effects of other analgesics). The risk of renal disease was also increased in daily users of acetaminophen; after adjustment for the use of aspirin and phenacetin, the odds ratio was 3.21 (confidence interval, 1.05 to 9.80). There was no increased risk in daily aspirin users (adjusted odds ratio, 1.32; confidence interval, 0.69 to 2.51). The risks with daily use of either phenacetin or acetaminophen changed little after adjustment for diabetes, hypertension, and the indication for analgesic use. We conclude that the long-term, regular use of phenacetin may increase the risk of chronic renal disease. The long-term, daily use of acetaminophen, the major metabolite of phenacetin, is associated independently with an increased risk of chronic renal disease. We could find no increased risk in daily users of aspirin.     

Hypoxia induces renal tubular epithelial cell apoptosis in chronic renal disease.

Renal tubular atrophy characterizes chronic progressive renal disease, but the molecular mechanisms of renal tubular cell (RTC) deletion are unclear. Because glomerular sclerosis leads to impaired peritubular blood flow, we tested the hypothesis that chronic hypoxia contributes to RTC apoptosis. Tubule hypoxia in mice with progressive renal disease (Os/+) was assessed by injecting EF5, a nitroimidazole compound that preferentially binds to cells undergoing anaerobic metabolism. Hypoxic tubules, as determined by direct immunofluorescence with anti-EF5 antibodies, were identified in kidneys from Os/+ mice, but not in age-matched controls (+/+) at 12 weeks, coincident with the onset of glomerular pathology. Hypoxia can cause apoptosis, but apoptotic RTCs were rare and equivalent in number in 12 week Os/+ and +/+ kidneys. However, by 16 weeks apoptotic RTCs were significantly more frequent in Os/+ versus +/+ mice, demonstrating that tubule hypoxia preceded RTC apoptosis. Importantly, apoptotic RTCs co-localized to hypoxic, but not normoxic tubules, indicating that tubular atrophy may result from hypoxic stimulation of RTC apoptosis. We have previously demonstrated enhanced, diffuse expression of the Fas apoptosis receptor in Os/+ tubules, providing a potential intermediary between hypoxia and apoptosis. To determine whether hypoxia stimulates Fas-dependent apoptosis, RTCs were cultured within a hypoxia chamber or in the presence of the cyanide analog, sodium azide. Both in vitro hypoxic conditions stimulated RTC plasma membrane Fas expression, and caused RTC apoptosis upon ligation with agonistic Fas antibodies. The data suggest that in the context of progressive renal disease, chronic hypoxia stimulates Fas-dependent RTC apoptosis, which represents the first definitive link between hypoxia and tubular atrophy. We believe that hypoxic induction of RTC apoptosis provides a unifying mechanism for the pathogenesis of tubular atrophy, and this paradigm identifies novel targets for chronic renal failure therapy.     

Measures of renal function in patients with cisplatin-related chronic renal disease.

Twenty-seven patients with advanced stage refractory ovarian cancer were studied to determine if chronic stable cisplatin-related renal dysfunction was present. Medical histories were examined to determine the types of therapy previously received as well as the total previous platinum doses received that ranged from 200 to 2,100 mg/m2. Standard assessments of renal function were made prior to administering current chemotherapy or immunotherapy to the patient, which included 24-hour creatinine clearance, serum creatinine, and blood urea nitrogen (BUN). For patients with a 24-hour creatinine clearance of less than 60 mL/minute, serum creatinine was highly variable (range: 0.9 to 2.0 mg/dL) and was not related to the degree of diminution in the 24-hour creatinine clearance value. Conversely, for patients with a serum creatinine of less than 1.5, the 24-hour creatinine clearance values varied by almost three-fold, ranging between 46 and 120 mL/minute. Two patients with serum creatinines of less than 1 had creatinine clearances of less than 50 mL per minute. Similarly, BUN measurements did not correlate with 24-hour creatinine clearance values, and the 24-hour creatinine clearance value was not related to the total cumulative platinum dose. We conclude that patients who receive substantive doses of cisplatin may experience chronic stable cisplatin-related renal dysfunction and that serum creatinine cannot be relied on to assess the degree of renal compromise. In such patients, we recommended that the 24-hour creatinine clearance value should be used when medical management is influenced by renal function.     

Kidney dendritic cells in acute and chronic renal disease

Dendritic cells are not only the master regulators of adaptive immunity, but also participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney, and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. Here we summarize the current knowledge on the role of kidney dendritic cells that has been obtained from the study of murine models of renal disease.     

Erythrocyte transketolase activity in patients with chronic renal disease

B1 vitamin deficiency was studied by the erythrocyte enzyme activation test in patients with chronic uraemia. Transketolase activity was measured in the erythrocyte haemolysates of 14 patients with chronic uraemia and in 16 healthy controls in the presence of TPP and following TPP saturation. The magnitude of activity increases as a result of TPP saturation which is probably indicative of an insignificant thiamine deficiency in patients with chronic uraemia.