Cooper J D, Lazarowitz V C, Arieff A I
J Clin Invest. 1978 Jun;61(6):1448-55. doi: 10.1172/JCI109064.
Neurological abnormalities are a major cause of morbidity in patients with renal failure. The pathophysiology of these neurological changes is unclear, and the effects on them of dialysis and return of renal function have not been well studied. Studies were done in 31 patients who had acute renal failure (ARF), all of whom were either treated with dialysis within 5 days or did not survive. Studies on these patients included the electroencephalogram (EEG), motor nerve conduction velocity, and plasma Ca(++) and parathyroid hormone (PTH) levels. Studies were done at the time ARF was diagnosed, after stabilization on dialysis, during the diuretic phase of ARF, and 3 mo after recovery from ARF. In 16 patients with acute or chronic renal failure who did not survive and in nine patients without renal disease who died, measurements were made in brain of content of Na(+), K(+), Cl(-), Ca(++), Mg(++), and water. In patients with ARF for less than 48 h, despite the fact that there were only modest increases in plasma urea and creatinine, there were striking abnormalities in the EEG. The percent EEG power < 5 Hz+/-SE was 41+/-8% (normal = 2+/-1%), whereas the percent of frequencies > 9 Hz was only 22+/-6% (normal = 62+/-3%). These changes were unaffected by dialysis, but became normal with return of renal function and remained normal at 3 mo follow-up. The motor nerve conduction velocity was unaffected by either ARF or dialysis. In patients with ARF, the brain Ca(++) was 46.5+/-3.2 meq/kg dry wt, almost twice the normal value of 26.9+/-1.0 meq/kg dry wt (P < 0.001). The plasma PTH level was 3.2+/-0.6 ng/ml (normal < 1.5 ng/ml, P < 0.01). The increased brain Ca(++) was not related to an increased plasma (Ca(++)) (PO(4) (---)) product (r(2) = 0.14, P > 0.05). There was a small but significant decrement in brain Na(+) (P < 0.05), but brain water, K(+), and Mg(++) were unaffected by ARF.Thus, in patients with ARF for less than 48 h, the EEG is grossly abnormal and there are elevated levels of PTH in plasma. The PTH appears to have a direct effect on the brain, resulting in an increased brain Ca(++) content. The EEG abnormalities are unaffected by dialysis, but they become normal with return of renal function and remain normal after 3 mo follow-up. Thus, PTH may be a major uremic toxin, demonstrating evidence for central nervous system toxicity when there are only minimal abnormalities of other biochemical markers of ARF.
神经功能异常是肾衰竭患者发病的主要原因。这些神经功能改变的病理生理学机制尚不清楚,透析及肾功能恢复对其影响也未得到充分研究。对31例急性肾衰竭(ARF)患者进行了研究,所有患者均在5天内接受透析治疗或死亡。对这些患者的研究包括脑电图(EEG)、运动神经传导速度以及血浆钙离子(Ca(++))和甲状旁腺激素(PTH)水平。研究在ARF确诊时、透析稳定后、ARF利尿期以及ARF恢复后3个月进行。对16例未存活的急性或慢性肾衰竭患者以及9例无肾脏疾病的死亡患者,测定了脑内钠离子(Na(+))、钾离子(K(+))、氯离子(Cl(-))、钙离子(Ca(++))、镁离子(Mg(++))含量及水分。在ARF病程小于48小时的患者中,尽管血浆尿素和肌酐仅有适度升高,但脑电图出现显著异常。脑电图功率<5Hz±标准误的百分比为41±8%(正常为2±1%),而频率>9Hz的百分比仅为22±6%(正常为62±3%)。这些改变不受透析影响,但随着肾功能恢复而恢复正常,且在3个月随访时仍保持正常。运动神经传导速度不受ARF或透析影响。ARF患者脑内Ca(++)含量为46.5±3.2meq/kg干重,几乎是正常水平26.9±1.0meq/kg干重的两倍(P<0.001)。血浆PTH水平为3.2±0.6ng/ml(正常<1.5ng/ml,P<0.01)。脑内Ca(++)升高与血浆(Ca(++))(PO(4) (---))乘积增加无关(r(2)=0.14,P>0.05)。脑内Na(+)有小幅但显著下降(P<0.05),但脑内水分、K(+)和Mg(++)不受ARF影响。因此,在ARF病程小于48小时的患者中,脑电图严重异常且血浆PTH水平升高。PTH似乎对脑有直接作用,导致脑内Ca(++)含量增加。脑电图异常不受透析影响,但随着肾功能恢复而恢复正常,且在3个月随访后仍保持正常。因此,PTH可能是一种主要的尿毒症毒素,在ARF其他生化指标仅有轻微异常时就显示出对中枢神经系统的毒性证据。