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所有中文翻译均以英文原文为最终参照

 

Cat Renal Health

猫的肾健康

 

Key Message

关键信息

​WALTHAM research has contributed to the understanding of the role of diet in cats with chronic kidney disease by:

威豪致力于猫的慢性肾疾病领域研究工作的方式包括:

 

Demonstrating that a diet with restricted protein and phosphorus levels can reduce rates of clinical deterioration in cats suffering from naturally occurring chronic kidney disease.

  • Showing that an appropriate diet can help to control renal secondary hyperparathyroidism in cats with chronic kidney disease.
  • Developing the first clinical diet proven to increase the lifespan of cats after diagnosis of chronic kidney disease.
  • Determining predictors of azotaemia (urine containing high levels of nitrogen-containing products, for example urea) which may enable early identification of cats at risk of chronic kidney disease.
  • 证明低蛋白与低磷猫粮能够降低猫的自然慢性肾病临床恶化率。
  • 表明适当的猫粮有助于对猫的继发性甲状旁腺功能亢进合并慢性肾病进行控制。
  • 首次开发出被证明具有延长患有慢性肾病的猫寿命功能的临床猫粮。
  • 确定氮血症的预测因子(尿液中含有高浓度的含氮物质,如尿素),从而使早期发现猫的慢性肾病发病风险成为可能。

 

Background

背景

 

Chronic kidney disease represents the end stage of a variety of renal diseases. It is generally progressive and is ultimately fatal. The diagnosis is based on azotaemia (urine containing high levels of nitrogen-containing products, for example urea) combined with an inability to produce concentrated urine. Advanced kidney disease results in uraemia (urine high in nitrogenous waste products), and is characterised by polyuria (abnormally large volume of urine) and polydipsia (excessive thirst), anorexia and weight loss, lethargy, vomiting, and pallor and ulceration of the mucous membranes. Although existing renal damage is irreversible, quality of life can be improved by correcting biochemical abnormalities and alleviating some of the clinical signs of the disease. 

 

慢性肾病指多种肾病的末期阶段。慢性肾病通常会不断发展并最终具有致命性。慢性肾病的诊断依据是氮血症(尿液中含有高浓度的含氮物质,如尿素)以及无法产生浓缩尿的情况。晚期肾病能够导致尿毒症(含氮废物较高的尿液),特征包括多尿症(尿量异常增大)与烦渴(过度口渴)、厌食与体重减轻、嗜睡、呕吐、黏膜苍白与溃疡。尽管肾损害具有不可逆性,但纠正生化不正常指标与减轻部分临床疾病症状能够使患者的生活质量得到改善。

 

Chronic kidney disease is common in older cats. When a cohort of geriatric cats (9 years of age or older) were followed in a London-based study, 30.5% (29/95) developed azotaemia (Jepson et al. 2009). 

慢性肾病常见于老龄猫。一项在伦敦进行的研究对一群老龄猫(年龄不低于9周岁)进行了跟踪调查,结果发现其中有30.5%(29/95)的猫患有氮血症(Jepson 等,2009年)。

 

Diet is the cornerstone of the conservative management of chronic kidney disease. An appropriate diet can ameliorate clinical signs of uraemia, minimise electrolyte and vitamin and mineral disturbances, and contribute to slowing disease progression. Diets designed for managing chronic kidney failure commonly have modified amounts of calcium, sodium, potassium, and water-soluble vitamins, as well as dietary energy and fat. However, phosphate and protein restriction have been the subjects of much study. 

 

慢性肾病保守治疗方法的基础是饮食控制。适当的饮食能够减轻尿毒症的临床症状,尽可能降低电解质与维生素与矿物质含量失调的程度,并有助于延缓慢性肾病的进展。专门为慢性肾衰竭设计的猫粮中的钙、钠、钾、水溶性维生素以及能量与脂肪含量均经过调整。目前,磷酸盐与蛋白的含量限定水平也已经成为很多研究的对象。

 

When renal function is compromised, phosphate is not excreted very efficiently and is retained in the body. Phosphate retention causes an adaptive increase in parathyroid hormone secretion and subsequently secondary renal hyperparathyroidism that affects metabolism. Dietary phosphate restriction increases the survival of dogs with reduced renal mass (Finco et al. 1992) and reduces renal fibrosis, mineralisation, and mononuclear cell infiltration in cats with reduced renal mass (Ross et al. 1982). However, the mechanism of the benefit is the subject of debate. 

 

肾功能受损之后,身体即无法高效排泄磷酸盐,因此导致磷酸盐滞留体内。磷酸盐滞留会导致身体内甲状旁腺激素分泌的自适应性增加,进而导致继发性甲状旁腺机能亢进,从而影响机体的新陈代谢。限制饮食中的磷酸盐含量能够提高患有肾脏小肿块的狗的存活期 (Finco等,1992年),并降低患有肾脏小肿块的猫的肾脏纤维化与矿化程度以及单核细胞浸润程度(Ross等,1982年)。但是,上述疗效机理目前仍颇有争议。

 

When dietary protein is consumed glomerular filtration rate increases, dependent on the quantity and nature of the dietary protein. In rats with reduced renal mass, restricting dietary protein intake limits proteinuria, reduces renal lesions, and increases survival (Hostetter et al. 1986; El-Nahas et al. 1983). In cats there has been much debate about the potential benefit of protein restriction (see Finco et al. 1998). However, although marked proteinuria is often not a feature of feline chronic renal disease, the low concentrations that are found are prognostic (Syme et al. 2006).

 

食物蛋白被摄入消化时,肾小球滤过率会随之升高,升高的具体程度取决于日粮蛋白的数量与性质。对于患有肾脏小肿块的大鼠,较低的日粮蛋白含量有助于限制其蛋白尿程度,降低肾损害程度,并能够增加存活期(Hostetter 等,1986年; El-Nahas等,1983)。

 

Why WALTHAM is Interested

Chronic kidney disease is common in older cats. Previously, there had been little work done on the dietary management of feline chronic kidney failure, with recommendations based only on observations in other species.

为何威豪有兴趣从事该领域的研究

慢性肾病是老龄猫的常见疾病。之前,关于猫的慢性肾衰竭饮食管理方面的研究非常有限,相关建议也仅仅建立对其他物种的观察结果之上。

 

Approach

方法

 

Controlled clinical studies were undertaken to investigate the benefits of a diet formulated for renal health in cats with naturally occurring chronic kidney disease, in terms of clinical signs, parathyroid hormone level and survival.

Studies were undertaken to demonstrate the benefits of dietary intervention before renal function deteriorates too far and the factors predicting future azotaemia were also investigated.

为了研究以患有自然慢性肾病的猫的肾健康为对象的特制饮食的临床受益情况,研究人员进行了对照临床试验,研究的对象包括临床症状、甲状旁腺素和存活期。

研究人员还进行了旨在证明肾功能过度恶化之前饮食干预的作用试验,并进行了氮血症预测因子的研究。

 

Discovery (Diet Clinical)

An appropriate diet slows the rate of clinical deterioration of cats with chronic kidney disease

研究发现(临床治疗性食物)

适当的饮食能够延缓猫的慢性肾病的临床恶化率

 

This study was a collaboration between WALTHAM, Ecole Nationale Veterinaire d'Alfort, Paris, and Strathclyde University, Glasgow. A total of 35 client-owned cats were recruited, all with naturally-occurring chronic kidney disease, defined as serum creatinine ≥167 μmol/L and/or serum urea nitrogen ≥21 mmol/L, with urine specific gravity (Harte et al. 1994). The cats were randomly allocated to one of two diets for 24 weeks: a control diet providing levels of protein and phosphorus at the low end of normal products (23.6 g protein and 0.48 g phosphorus/MJ metabolisable energy) or a diet containing restricted amounts of these nutrients (15.1 g protein and 0.23 g phosphorus/MJ metabolisable energy). The majority of cats receiving the control diet continued to lose weight, whilst those fed the restricted phosphorus/protein diet showed an increase in mean body weight (Harte et al. 1994). The deterioration in halitosis, gingivitis, appetite, and body condition was considered to be less in the cats fed the restricted phosphorus/protein diet (Harte et al. 1994). Mean serum urea nitrogen and creatinine levels were not significantly different between the two groups at baseline, but both increased in the control group; in contrast, both decreased in the cats fed the restricted phosphorus/protein diet (Harte et al. 1994). Similarly, serum phosphate increased in the control group and decreased in the cats fed the restricted phosphorus/protein diet (Harte et al. 1994).  

该研究由威豪、巴黎阿尔夫尔国立兽医学校以及格拉斯哥斯特莱斯克莱德大学合作进行。研究共招募35只客户养的宠物猫作为研究对象,这些猫全部患有自然慢性肾病,诊断标准为血清肌酸酐≥167 μmol/L和/或血清尿素氮≥21 mmol/L,且尿液比重<1.036(Harte等,1994)。研究人员将观察猫随机分组并被喂食两种猫粮中的一种,喂食时间为24周,这两种猫粮分别为:对照猫粮:能够提供相当于正常猫粮下限含量的蛋白和磷(23.6克蛋白质与0.48克磷/兆焦耳代谢能),以及限制上述营养素含量的猫粮(15.1克蛋白与0.23克磷/兆焦耳代谢能)。在试验过程中,大多数被喂食对照饲粮的猫的体重持续降低,而被喂食限磷/蛋白猫粮的猫的平均体重却有所增加(Harte等, 1994)。研究人员发现,被喂食限磷/蛋白猫粮的猫的口臭、齿龈炎、食欲以及身体状况恶化程度均有所减轻。两组试验猫在入组时的平均血清尿素氮以及肌酸酐含量值没有显著差异,但对照组在试验过程中上述两值均有所升高;被喂食限磷/蛋白猫粮的猫在试验过程中上述两值却有所降低(Harte等,1994)。同样地,对照组猫的血磷值有所升高,而被喂食限磷/蛋白猫粮的猫的血磷脂有所降低(Harte等,1994)。

 

This study showed that cats with chronic kidney disease can benefit from being fed an appropriate diet, with an apparent slowing of clinical deterioration.

该研究表明,喂食营养素适当的猫粮能够为患有慢性肾病的猫带来收益,使其临床症状的恶化程度明显减缓。

 

Discovery (Diet and Parathyroid Hormone)

An appropriate diet can reduce parathyroid hormone levels in cats with chronic kidney disease

研究发现(饮食与甲状旁腺素)

适当的猫粮能够降低患有慢性肾病的猫的甲状旁腺素水平。

 

Renal secondary hyperparathyroidism is a common complication of chronic kidney disease in cats and can result in bone pain and soft tissue calcification. In other species it is treated with dietary phosphate restriction and intestinal phosphate binders, although this had never been investigated in cats with hyperparathyroidism secondary to naturally occurring chronic kidney disease.

肾病继发性甲状旁腺功能亢进是一种常见的猫慢性肾病并发症,该病能够导致骨痛与软组织钙化。在治疗该疾病方面,对于其他物种往往采用限制饮食中肠道磷结合剂的疗法,但目前尚未对患有自然慢性肾病合并继发性甲状旁腺机能亢进的猫进行上述疗法研究。

 

In this study, carried out in collaboration with the Royal Veterinary College, London, 23 client-owned cats with stable naturally occurring chronic kidney disease (defined as plasma creatinine >180 μmol/L) were recruited (Barber et al. 1999). They were fed a diet with restricted protein (22.1–24 g/400 kcal) and phosphorus (0.29–0.41 g/400 kcal) content or (if they would not accept this) a normal diet (48.4 g protein and 1.9 g phosphorus per 400 kcal). Cats fed the restricted phosphorus/protein diet had significant reductions in plasma phosphate and parathyroid hormone levels over 5 months (Figure 1), with only 2/14 cats requiring phosphate binders (Barber et al. 1999). Euparathyroidism was achieved in 8 cats in the restricted phsphorus/protein group (Barber et al. 1999). In contrast, in the control group, parathyroid hormone levels increased in 7/8 cats (Barber et al. 1999).

该项研究系伦敦皇家兽医学院与威豪合作进行。该研究招募患有自然肾病(病情稳定)的客户宠物猫(诊断标准为血浆肌酐>180 μmol/L)作为试验对象(Barber等,1999年)。在试验中,研究人员向试验猫喂食限蛋白(22.1–24克/400 千卡)限磷(0.29–0.41克/400 千卡)猫粮或者(如果试验猫愿意食用)正常猫粮(48.4 克蛋白与1.9克磷/400千卡)。试验发现,在5个月中,被喂食限磷/蛋白猫粮的猫血浆中磷与甲状旁腺素的含量显著降低(图1),其中只有2/14的猫需要被喂食磷结合剂(Barber等,1999年)。在被喂食限磷/蛋白猫粮的试验组猫中,8只达到了甲状腺功能良好状态 (Barber等,1999年) 。与此相反,在对照组的8只猫中,有7只的甲状旁腺素含量出现上升。

图片来源:玛氏宠物护理学院

Figure 1: Mean ± SEM change in plasma creatinine, urea, phosphate and parathyroid hormone levels in cats with chronic kidney disease fed phosphorus/protein-restricted diets (squares, n=14) or normal diets (circles, n=8) (Barber et al. 1999). NS, not significant. * denotes no significant difference between groups at day 0. P values show significant difference compared with respective baseline

图1:患有慢性肾病的猫在被喂食限磷/蛋白猫粮(以方框表示,n=14)或正常猫粮(以圆圈表示,n=8)后的血浆中肌酸酐、尿素、磷酸盐以及甲状旁腺素含量的平均值±平均数标准误差(Barber 等,1999)NS表示不显著;*表示在试验第0天两组之间未见显著差异。P值表示相对于入组时的对应值具有显著差异性。

 

This study showed that an appropriate diet, with phosphate binders if required, can reduce and normalise plasma parathyroid hormone levels in cats with chronic kidney disease. This research contributed to the lead author of this study (Dr. Penny Barber) winning the inaugural International Renal Interest Society (IRIS) award in 2000.

该研究表明,适当的饮食(如必要,可添加磷结合剂)有助于降低患有慢性肾病的猫的血浆中甲状旁腺素含量水平并使其恢复正常。凭借该项研究成果,该研究的首席作者(Penny Barber博士)在2000年获得了首届国际肾脏权益组织(IRIS)奖的研究成果奖。

 

Discovery (Diet Survival)

研究发现(存活期饮食)

WALTHAM developed the first diet proven to increase the lifespan of cats diagnosed with chronic kidney disease.

威豪已经成功开发出第一种被证明有助于延长患有慢性肾病的猫的寿命的猫粮。

 

Dietary phosphorus restriction increases survival in dogs with reduced renal mass (Finco et al. 1992). However, this was the first time the effect of phosphorus restriction on survival had been prospectively studied in cats with naturally-occurring chronic kidney disease (Elliott et al. 1998; Elliott et al. 2000).

限磷饮食能够提高患有RRM(Reduced Renal Mass)的狗的存活期(Finco等,1992年)。然而,以限磷猫粮对患有自然慢性肾病的猫的影响为主题的前瞻性研究尚属首次。

 

In this prospective study, carried out in collaboration with the Royal Veterinary College and the University of Edinburgh, 50 client-owned cats with stable naturally-occurring chronic kidney disease (defined as plasma creatinine >180 μmol/L) were followed from their time of diagnosis (Elliott et al. 2000). They were fed a diet with restricted protein (13.2–14.4 g/MJ) and phosphorus (0.16–0.25 g/MJ) content or (if they would not accept this) a normal (28.9 g protein and 1.14 g phosphorus per MJ) diet. The restricted phosphorus/protein diet resulted in reduced plasma phosphate and urea concentrations, and prevented the increase in parathyroid hormone level exhibited by the cats fed the control diet (Figure 2. Elliott et al. 2000).

此次前瞻性研究由威豪与皇家兽医学院以及爱丁堡大学共同开展。研究以患有稳定性自然肾病(血浆肌酸酐>180 μmol/L)的宠物猫为试验对象并从其被确诊之日开始对其保持跟踪调查(Elliott 等,2000年)。这些猫被喂食限蛋白(13.2–14.4 克/兆焦)限磷(0.16–0.25克/兆焦)猫粮,或者(如果愿意食用)正常猫粮(28.9 克蛋白与1.14克磷/千焦)。被喂食限磷/蛋白猫粮后,试验猫血浆中的磷与尿素浓度均有所降低,并且(与被喂食对照猫粮的对照组试验猫相比)能够提高猫体内甲状旁腺素的含量。

图片来源:玛氏宠物护理学院

Figure 2: Plasma phosphate and parathyroid hormone concentrations in cats with chronic kidney disease fed a restricted phosphorus/protein diet (Elliott et al. 2000). Graphs show mean ± SEM initial and mid-survival values. Open columns are the normal phosphorus group and hatched columns the phosphorus restricted group. * denotes significant difference between groups (P<0.01), # denotes significant difference for that group versus their value at diagnosis (P<0.02)

2患有慢性肾病的猫在被喂食限磷/蛋白猫粮后体内血浆中的磷与甲状旁腺素浓度(Elliott等,2000)。上图中显示的是各参数初始期与中期存活期值的平均数±平均数标准误差。空白柱与阴影柱分别表示喂食磷含量正常猫粮的试验组与喂食限磷猫粮的试验组。*表示两组之间具有显著差异性(P<0.01)#表示该组相应参数值与其确诊时相比出现显著差异性(P<0.02)

 

The effect on survival is shown in Figure 3, with median survival was 633 days for the cats fed the restricted phosphorus/protein diet, and 264 days for the cats fed the control diet (Elliott et al. 2000). Phosphate binders were required in only 10/29 of the cats in the restricted phosphorus/protein group (Elliott et al. 2000).

图3显示的是饮食对于存活情况的影响情况。其中,被喂食限磷/蛋白饲粮的猫的存活期中值为633天,被喂食对照猫粮的猫的存活期中值为264天(Elliott 等,2000)。在被喂食限磷/蛋白猫粮的试验组的29只猫中,仅有10只需要服用磷结合剂(Elliott等,2000年)。

图片来源:玛氏宠物护理学院

Figure 3: Feeding cats with chronic kidney disease a restricted phosphorus/protein diet increases their survival (Elliott et al. 2000). Graph shows Kaplan-Meier survival curves, with dotted line for normal phosphorus diet group and solid line representing restricted phosphorus group. Comparison of curves by log-rank analysis showed significant difference (P=0.0036)

图3:向患有慢性肾病的猫喂食限磷/蛋白猫粮能够延长其存活期(Elliott等,2000)。上图显示的是Kaplan-Meier生存曲线,其中的虚线表示被喂食磷含量正常猫粮后猫的存活期,实现表示的是被喂食限磷猫粮后猫的存活期。通过对数秩分析对曲线进行的比较结果显示两组的存活期差异具有显著性。

 

This study showed that an appropriate diet, with phosphate binders if required, controls hyperphosphataemia and secondary renal hyperparathyroidism, and increases the survival time of cats with chronic kidney disease.

该研究表明,适当的饮食(如必要,可添加磷结合剂)有助于控制高磷酸盐血症与肾病继发性甲状旁腺功能亢进,并能够延长患有慢性肾病的猫的存活期。

 

Discovery (Predictors)

Plasma and urinary variables can predict azotaemia and might provide early identification of cats at risk of future chronic kidney disease

研究发现(预测因子)

血浆与尿液的各种变量可以作为对氮血症进行预测的依据,而且也是早期发现存在今后患上慢性肾病风险的猫的依据。

 

Appropriate dietary intervention that provides additional support for renal function before deterioration goes too far is an attractive strategy. Traditionally, diagnosis is made on finding azotaemia and the inability to concentrate urine.  By the time a cat displays these signs renal function is already compromised.

采取适当的对肾功能具有辅助作用以防止其恶化的饮食干预疗法是非常具有吸引力的策略。传统上对慢性肾病的诊断依据是氮血症以及无法产生浓缩尿的情况,但如果猫表现出上述症状,则表明其肾功能已经受到损伤。

 

This prospective study, in collaboration with the Royal Veterinary College, London, aimed to identify early predictors of azotaemia in elderly cats (Jepson et al. 2009). A total of 118 client-owned non-azotemic elderly cats (9 years of age or older) were recruited and baseline clinical, biochemical and urinalysis variables recorded. The cats were followed up every 6 months until development of azotemia, death, or the study endpoint. Multivariable logistic regression was used to determine any relationship of baseline characteristics to subsequent azotaemia. The analysis showed that baseline plasma creatinine concentration with either baseline urinary protein to creatinine ratio (Model 1) or baseline urinary albumin to creatinine ratio (Model 2) were significant predictors of the development of azotaemia (Jepson et al. 2009).

该项研究系威豪与伦敦皇家兽医学院共同开展,研究目标是确定出老龄猫氮血症的早期预测因子(Jepson等,2009年)。研究共对118只客户的宠物猫进行研究,这些猫均为不患有氮血症的老龄猫(年龄不低于9周岁)。研究人员在其入组时对其临床、生化与尿液分析参数进行了记录。在试验中,研究人员对上述试验猫每6个月进行一次随访,直至其氮血症出现发展、试验猫死亡或研究结束。研究人员采用多变量逻辑回归法以测定入组时的各项参数特征与随后发生的氮血症之间的关系。分析结果表明,入组时的血浆肌酸酐浓度(尿蛋白与肌酐比值(模型1)或尿白蛋白与肌酐比值(模型2))可以作为氮血症发展的主要预测因子 (Jepson 等,2009年)。

 

This study suggests that straightforward plasma and urinary variables can predict azotaemia, and might provide early identification of cats at risk of future chronic kidney disease.

该研究表明,血浆与尿液的相关参数可直接用作预测氮血症的依据,并且还可能可以作为早期发现存在今后患上慢性肾病风险的猫的依据。

 

References (参考书目,略)