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Aluminum accumulation in plasma and tissues is a well-described complication among persons undergoing peritoneal dialysis or hemodialysis. Excess bone aluminum is associated with low bone formation rates and increased risk for fractures. Current recommendations for care of patients with end-stage renal disease include screening for aluminum toxicity with plasma aluminum levels; patients with levels below 40 microg/L are considered to be at low risk for aluminum bone disease (ABD). We examined data from the Toronto Renal Osteodystrophy Study to evaluate the performance of plasma aluminum levels in screening for ABD. Two hundred fifty-eight unselected patients undergoing peritoneal dialysis (n = 143) or hemodialysis (n = 115) underwent diagnostic bone biopsy and measurement of plasma aluminum level. Sixty-nine patients (26.7%) were identified as having ABD, defined as low or normal bone formation rates with 25% or more bone surface aluminum staining. Plasma aluminum level was strongly associated with the presence of ABD; the odds ratio was 1.4 for each increase of 10 microg/L (95%CI, 1.2, 1.6). However, only 50.1% of patients with a plasma aluminum level of 40 microg/L or greater had ABD, whereas 14.2% of patients with a level below this threshold also had ABD. Using this cutoff level of 40 microg/L, the sensitivity and specificity were 65.2% and 76.7%, respectively. We conclude that although there is a correlation between high aluminum levels and ABD, a patient's plasma aluminum level does not predict well the presence of ABD in spite of a relatively high prevalence of disease.

With the markedly reduced usage of aluminum salts in renal failure, parathyroid hormone (PTH) has become the major determinant of currently seen bone disease. Clinicians now must consider what PTH level should be sought. Too low a level may lead to the aplastic bone lesion (low turnover bone), and too high a level may cause osteitis fibrosa. Furthermore, conventional normal PTH levels may not be a suitable target because of the well-known resistance to PTH in uremic patients. In this report, we derive the PTH levels that best distinguish patients with low and high bone formation states from those with normal bone formation in a group of 175 dialysis patients without aluminum toxicity. Using bone histological parameters, we propose that ideally PTH levels should be maintained between 10 pmol/L (100 pg/mL) and 20 to 30 pmol/L (200 to 300 pg/mL) in chronic dialysis patients, levels two to four times the upper limit of values found in normal subjects.

Chronic nephrotoxicity is a major complication in high-dose cyclosporine treatment. We examined the glomerular filtration rate, renal plasma flow, and kidney biopsies of 15 psoriatic patients treated with low-dose cyclosporine (< or = 5 mg/kg/d) for 30 months (25 to 35 months) 1 month after drug withdrawal. The mean (95% confidence interval) age of the patients in the study was 44 years (38 to 50 years). Their serum creatinine levels pretreatment and at the time of the study were 0.94 mg/dL (0.85 to 1.0 mg/dL) and 1.2 mg/dL (1.1 to 1.3 mg/dL). Seven patients had a decreased glomerular filtration rate and four of them also had a reduced renal plasma flow, below the 2.5 percentile of normal. Four patients had moderate tubulointerstitial scarring and arteriolopathy, while the remaining patients had mild structural abnormalities. The severity of acute nephrotoxicity during treatment and chronic structural injury were highly correlated (r = 0.81; P < 0.0003). Recurrent episodes of severe acute nephrotoxicity (defined as reversible increase of serum creatinine > 90% of baseline value) was a marker for moderate chronic nephrotoxicity. No correlation was found between chronic structural injury and patient age, sex, pretreatment creatinine level, blood pressure (pretreatment or during treatment), cyclosporine dose and treatment duration, and cyclosporine blood levels. In seven patients continued on cyclosporine for another 12 months (10 to 14 months), repeat studies showed no interval changes. Despite 40 months (30 to 51 months) of treatment, all but one of these seven patients (with previous hypertension and atherosclerotic vascular disease) had mild functional and structural abnormalities. None had any severe acute nephrotoxicity at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine A (CyA) is known to cause hyperkalemia by impairing renal potassium excretion. However, the observation of transient and severe hyperkalemia occurring within 3 to 5 hours of CyA ingestion in several organ transplant patients led us to postulate that it might also cause a potassium efflux from the intracellular to the extracellular fluid space. We tested this hypothesis by studying 22 nondiabetic, renal transplant patients with stable renal function (serum creatine < 2.25 mg/dL) who were treated with CyA (CyA group; n = 14) or imuran and prednisone (STD group; n = 8). Eight CyA and four STD patients also were treated with a beta-blocker (BB). While at rest, fasting plasma potassium levels were sampled hourly in all patients from 8:00 am to 1:00 pm. All medications (including CyA and BBs) were given after the 8:00 am blood sampling. Venous pH, osmolality, insulin, aldosterone, epinephrine, norepinephrine, and CyA levels also were determined at 8:00 am, 11:00 am, and 1:00 pm. Urine was collected from 11:00 pm to 8:00 am prior to the study (period I) and from 8:00 am to 1:00 pm during the study (period II) for measurement of potassium excretion (standardized to a 5-hour period). A significant increase in serial plasma potassium levels was noted in the CyA + BB group only (P = 0.0006 by repeated measures analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)