Chiz‐Tzung Chang, Chin‐Herng Wu, Chih‐Wei Yang, Jeng‐Yi Huang, Mai‐Szu Wu, Creatine monohydrate remedy alleviates muscle cramps related to haemodialysis, Nephrology Dialysis Transplantation, Quantity 17, Situation 11, November 2002, Pages 1978–1981, https://doi.org/10.1093/ndt/17.11.1978
Summary
Introduction
Painful muscle cramps typically complicate haemodialysis. They could happen in 35–86% of haemodialysis sufferers [1] and will be extreme sufficient to compromise haemodialysis remedy [2]. The precise mechanism of intradialysis muscle cramping continues to be unknown, and various palliative measures have been employed with out constant results [3]. Subnormal muscle metabolism is considered one of many main mechanisms underlying these muscle cramps [4]. Extreme dialysis ultrafiltration, intradialytic hypotension, or tissue hypoxia might result in an irregular utilization of vitality by muscle tissue and thus end in muscle cramps [5]. Creatine monohydrate has been used to extend muscle power and work efficiency in elite athletes [6]. It could trigger higher muscle metabolism by growing muscle creatine phosphate shops. Creatine phosphate can launch a phosphate group to ADP and switch it into ATP [7], which is the main supply of muscle vitality. With these info in thoughts, one may ask if administration of creatine monohydrate may alleviate the haemodialysis‐related muscle cramps (HAMC). To reply that query, we carried out a potential randomized examine to look at the impact of oral creatine monohydrate on HAMC.
Topics and strategies
Our cohort comprised 10 sufferers who had been on upkeep haemodialysis in a single dialysis unit in College Hospital (Chang Gung Memorial Hospital, Taipei, Taiwan), and who had skilled frequent intradialytic muscle cramps. After being enrolled within the examine and with their knowledgeable consent, the sufferers had been randomly assigned to the creatine and placebo teams, every of 5 sufferers. Every group comprised three females and two males, the creatine group with a median age of 57.4±18.3 years, and the placebo group with a median age of 56.0±7.9 years. No affected person was a smoker or alcohol person. The reason for finish‐stage renal illness in all 10 topics was continual glomerulonephritis, and none of them was on anti‐hypertensive drugs through the examine.
Hole‐fibre dialysers had been used with a bicarbonate‐primarily based dialysate, during which sodium focus was 140 mmol/l and calcium 1.75 mmol/l. A muscle cramp was outlined as a painful involuntary muscle contraction that lasted greater than 1 min through the dialysis [8]. An intradialytic hypotensive episode was a lower of greater than 15 mmHg in both systolic or diastolic blood strain. Following a double‐blind protocol, both creatine monohydrate powder (Oakdale NY) powder or placebo—12 g dissolved in 100 ml water—was given to the sufferers 5 min earlier than beginning haemodialysis. The doses had been administered by attending nurses with the intention to guarantee compliance. The prevalence of painful muscle cramps was recorded. Blood strain was measured each 30 min. Plasma creatinine, albumin, haematocrit, and Kt/V had been checked after 4 weeks of remedy. Kt/V was calculated as described by Jackson [9].
To additional verify that any noticed change was associated to the administration of creatine monohydrate, the identical medical and laboratory parameters had been adopted for an extra 4 weeks, thought-about as a washout interval.
Outcomes are expressed as means±SD. Notable variations between the 2 teams had been analysed by Scholar’s t‐take a look at and one‐means ANOVA. We used the SPSSTM program for statistical evaluation. A P worth <0.05 was thought-about vital.
Outcomes
The baseline haemodynamic and biochemical parameters earlier than creatine monohydrate or placebo remedy had been comparable in each teams (Desk 1). No improve in dry weight was discovered within the creatine group after creatine monohydrate remedy (earlier than vs after: 63.9±18.3 vs 63.9±18.3 kg, P>0.05). There was no vital change within the pre‐dialysis blood pressures and ultrafiltration charges. The prevalence of a hypotensive episode was barely decreased within the creatine group, however with out statistical significance (management vs creatine: 7.2±1.8 vs 5.8±2.6 instances/4 weeks, P>0.05). These outcomes point out that quick‐time period oral creatine monohydrate consumption didn’t induce vital haemodynamic adjustments throughout haemodialysis. The Kt/V, serum albumin, and haematocrit didn’t change within the teams both earlier than or through the remedy (Desk 1). The information steered that creatine monohydrate didn’t affect the prescribed dialysis dosage, dietary standing, and erythropoiesis in our sufferers. The episodes of muscle cramps had been decreased by 60% through the remedy interval within the creatine group (management vs creatine: 6.4±0.9 vs 2.6±1.8 instances/4 weeks, P<0.05). We did not observe any decrease in cramps in the placebo group (control vs placebo: 6.6±1.1 vs 6.2±0.8 times/4 weeks, P>0.05) (Determine 1). Serum creatinine elevated by 16% within the creatine group (management vs creatine: 10.7±3.2 vs 12.4±3.2 mg/dl, P<0.05) (Desk 1). The rise in serum creatinine was not related to anorexia, nausea, vomiting, or different uraemic signs. To additional verify that the noticed impact comes from creatine, we continued to observe the sufferers after remedy interval for an extra 4 weeks, thought-about as a washout interval. Throughout that 4‐week washout interval, the incidence of muscle cramps within the creatine group elevated to earlier ranges (6.2±0.8 instances/4 weeks) (Determine 1). This incidence is sort of the identical as that prevalent earlier than remedy (washout vs earlier than: 6.2±0.8 vs 6.4±0.9 instances/4 weeks). All different parameters of the washout interval had been equal to these earlier than remedy (Desk 1). Serum creatinine returned to pre‐remedy baseline values after the washout interval within the creatine group (washout vs earlier than: 10.2±3.0 vs 10.7±3.2 instances/4 weeks) (Determine 2).
There have been no noticed aspect‐results reminiscent of nausea or vomiting through the 4‐week remedy interval. No nausea and vomiting appeared through the 4‐week remedy interval in both the placebo or the creatine teams. Serum GPT ranges had been the identical earlier than and through creatine monohydrate remedy (15.5±3.6 vs 14.4±2.7 IU/l). 4 of the 5 sufferers within the creatine group requested to proceed the creatine monohydrate remedy after the tip of the examine.Dialogue – “does creatine cause cramps”
Muscle cramp is without doubt one of the commonest and uncomfortable issues skilled throughout haemodialysis. The precise mechanism of those muscle cramps continues to be unknown. It’s typically related to intradialytic hypotension, extreme ultrafiltration, or elevation of serum creatine kinase [10]. The acute administration of this painful complication has included hypertonic glucose, saline, or mannitol with inconsistent and variable results [11]. Larger dialysate sodium concentrations additionally scale back the incidence of HAMC. Profiling of dialysate sodium and bicarbonate additionally reduces cramping considerably [2,5]. Lengthy‐time period administration of vitamin E [11], quinine [11], and l‐carnitine [12] have additionally been used to lower the cramp however with equivocal outcomes. These brokers have in frequent the results of accelerating muscle vitality utilization and power. ATP splits into ADP and phosphate and liberates the vitality for muscle work. Irregular muscle vitality metabolism with subsequent lactic acid formation could also be the reason for muscle weak spot and painful muscle cramping [13].
Creatine monohydrate has lengthy been utilized by elite athletes to extend muscle mass and enhance efficiency [14]. It could improve muscle phosphocreatine shops and switch its phosphate group to ADP when muscle tissue want vitality [15]; the necessity for anaerobic era of ATP by way of the lactate pathway will probably be decreased [16], and the muscle membrane will be stabilized and cramps lowered as muscle vitality utilization is improved [17].
In our examine, creatine monohydrate considerably decreased the incidence of HAMC. There was no variations in dry weight, pre‐dialysis blood strain, ultrafiltration price, and hypotension episodes within the creatine group earlier than remedy or through the remedy, and washout intervals. Haemodynamic components had been equivalent within the two teams. The outcomes point out that haemodynamic change didn’t play a job within the noticed impact of creatine on muscle cramping. We imagine that the discount in muscle cramping might come from higher utilization of vitality within the muscle.
Paradoxically, creatine monohydrate can result in muscle cramp when utilized in people with regular renal perform. The attainable mechanism of that aspect‐impact is the change of cell quantity induced by creatine. Creatine might enter muscle cells and improve intracellular osmolality. The buildup of creatine inside muscle cells results in fluid shift from the extracellular compartment to intracellular areas. The ensuing shrinkage of extracellular fluid quantity causes muscle cramping [18]. This quantity‐shifting mechanism is perhaps compromised throughout haemodialysis by the concomitant managed ultrafiltration, which concurrently will increase extracellular osmolality and reduces extracellular fluid.
Serum creatinine might improve in sufferers with renal insufficiency who take creatine monohydrate [19]. There was a small improve in serum creatinine ranges in our sufferers. Nonetheless, they developed no anorexia, nausea, vomiting, or different uraemic signs in 4 weeks of creatine administration. Additional lengthy‐time period remark could also be indicated to find out the medical significance of elevated pre‐dialysis creatinine. There have been no adjustments in liver enzymes and serum albumin throughout 4 weeks of remedy, which can point out the absence of hepatic aspect‐results as reported within the literature [20]. Creatine monohydrate could also be secure in uraemic sufferers, at the very least for brief‐time period use.
We conclude that creatine monohydrate is perhaps used for the remedy of HAMC and that within the quick‐time period this agent is secure for sufferers on upkeep haemodialysis. Nonetheless, the variety of our sufferers was small and the observe‐up interval quick. Additional lengthy‐time period, giant‐scale research are necessary to verify the results and security of creatine monohydrate remedy in HAMC.
Correspondence and offprint requests to: Mai‐Szu Wu, Division of Nephrology, Chang Gung Memorial Hospital, 199 Tun Hwa North Highway, Taipei, Taiwan. E-mail: [email protected]
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