Traditional Chinese medicine combined with low-dose glucocorticoid for treating nephrotic syndrome:A case report

Shu-Ting Huang,Si-Chao Ding,Gan-Feng Xu

1Heilongjiang Academy of Traditional Chinese Medicine,Harbin 150036，China.

2Heilongjiang Provincial Hospital of Traditional Chinese Medicine,Harbin 150036,China.

Abstract Nephrotic syndrome(NS)is a common refractory clinical disease that can develop into end-stage renal disease(ESRD)if cannot be controlled.At present,in Western medicine,glucocorticoid or immunosuppressant drugs with heavy dose and long course are used for the therapy of NS.There are still few reports on the combined treatment of traditional Chinese medicine and low-dose glucocorticoid for NS.Here,we reported a case of a 48-year-old man diagnosed with NS,accompanied by severe pulmonary infection,abundant proteinuria,and pleural effusion.Integrated traditional Chinese and Western medicine was used as the therapeutic regimen of this patient.Traditional Chinese medicine(TCM)mainly focused on invigorating spleen and kidney,promoting blood circulation,removing blood stasis and promoting diuresis,and Chinese patent medicines or TCM immunosuppressants were given to consolidate the treatment.In Western medicine,small dose and short course glucocorticoids combined with symptomatic treatment were adopted.Delightfully,proteinuria subsided after 5 months treatment with integrated TCM and Western medicine and all laboratory reports were negative after 10 months,which has been normal so far(July 2019).This case report indicates that the combination of TCM and low-dose glucocorticoid is effective in curing NS,with low recurrence rate and few side effects.

Keywords: Nephrotic syndrome,Traditional Chinese medicine,Integrated Chinese and Western medicine,Treatment based on syndrome differentiation,Glucocorticoid

Background

Nephrotic syndrome(NS)is a group of clinical syndromes characterized by large amounts of proteinuria,edema,hypoalbuminemia and dyslipidemia,of which heave proteinuria is the characteristic manifestation and initial factor of NS,and the latter three are its consequences.Heave proteinuria(more than 3.5g/24h)and hypoalbuminemia(less than 30g/L)are necessary for the diagnosis of NS,which may lead to complications such as infection,thrombosis,embolism,acute renal injury,and disorders of protein and fat metabolism,etc.[1].Because NS develops rapidly and is prone to relapse,patients once exposed to predisposing factors such as infection,overwork,failure to take medicine on time etc.can lead to recurrence.So a convenient and effective treatment scheme with few side effects is particularly important.Currently,Western medicine mainly adopts high-dose glucocorticoid and immunosuppressive agents to cure NS.Long-term use of one agentor in combination with each other does have obvious side-effects and easy to relapse.Fortunately,TCM can give full play to its advantages,antagonize the side effects of glucocorticoid and immunosuppressants,and reduce recurrence.In this report,we will present a case patients with NS cured by TCM combined with low-dose glucocorticoids.After the treatment of integrated Chinese and Western medicine,the signs of pulmonary infection,large amount of proteinuria and high edema disappeared.And follow-up shows no recurrence so far.The treatment process is now reported as follows.

Case report

Brief introduction of illness

The patient,male,48 years old,is a retired Chinese soldier.He was admitted to local hospital on account of “whole body swelling for 3 days and aggravated for 1 day”.The patient is previously healthy.Foam urine was first noticed 3 years ago and was not taken seriously at that time.Symptoms including fever,cough,sputum,chest tightness and shortness of breath occurred 1 week ago after experiencing a common cold,but the symptoms were not relieved after taking oral medications(specific medications were unknown).3 days ago,serious pitting edema appeared in both lower limbs and eyelids,so he immediately went to the local hospital for treatment.On March 3,2018,the day after admission,relevant laboratory examinations were conducted.The blood routine showed that the total number of white blood cell was 9.87×10^9/L[normal range was(3.5-9.5)×10^9/L],the percentage of neutrophils was 80%(normal range: 40-75%).C-reactive protein(CRP)was 76.5mg/L [normal values ＜6.2 mg/L] and serum procalcitonin(PCT)was 0.169ng/mL [normal values ＜0.046 ng/mL].Liver function tests showed hypoproteinemia with total protein(TP)42g/L(normal: 65-85 g/L)and albumin(ALB)23g/L(normal: 40-56 g/L).Coagulation function test showed fibrinogen at 7.34g/L(normal:2-4 g/L).Complement C3 and C4 levels were in normal levels.In addition,total cholesterol(TC)was 9.47mmol/L(normal values 3.1-5.6 mmol/L),and low-density lipoprotein cholesterol(LDL-C)was 8.0mmol/L(normal levels 1.9-3.8 mmol/L).The 24-h urine protein test(24hUTP)was completed on March 5,showing severe protein loss up to 14.28g/24h(normal values ＜0.15g/24h).Computed tomography(CT)of lung revealed bilateral pneumonic changes such as lung markings increased,thickened,disordered and blurred,as well as blunt costophrenic angle and pleural effusion(Figure1).

The results of blood cell analysis,CRP and PCT all exceeded the normal range,suggesting that the patient was in a period of systemic inflammatory response.Combined with lung CT and clinical manifestations(fever,cough,chest pain,shortness of breath,etc.),it indicated that he picked up a nasty pulmonary infection.The typical characteristics of NS are massive proteinuria,severe edema,hyperlipidemia and hypoproteinemia.The relevant lab tests and patient’s clinical symptoms meet the diagnostic criteria of NS.Moreover,his abnormal excretion of urine protein far exceeded the normal range.Hence,the patient was diagnosed as “pulmonary infection and NS” by the local hospital initially and was given antibiotics(specific medicines were unknown).After 4 days of hospitalization,fever,cough,expectoration,and both lower extremities swelling still existed.Then he was transferred to a superior hospital for better treatment and arrived at our department(Department of Nephrology Ten,Heilongjiang Provincial Hospital of TCM)on the evening of March 6,2018.

Symptoms:fever,fatigue,palpitation,chest pain,chest shortness of breath,cough,occasional expectoration,nausea,lumbago,poor appetite,light sleep,as well as significant swelling in bilateral lower extremities and eyelids.

Diagnosis:TCM diagnosis: edema(deficiency of both spleen and kidney,syndrome of water immersion).Western medicine diagnosis: NS,pulmonary infection.

Treatment

Uniting the opinions of both physicians and nephrology experts,we decided to adopt the therapy of integrated Chinese and Western medicine.As the patient was crazy about exercising,he was advised to avoid strenuous activities and going out during hospitalization.In terms of diet,low-salt,low-fat and high-quality protein diet were required.Total urine volume and body weight should be measured every day.TCM decoctions were employed to invigorate spleen and kidney,relieve exterior syndrome and promote diuresis,activate blood and resolve stasis,according to the syndrome differentiation of TCM theory.The first prescription was as follows:Radix Astragali(Huang-qi)30g,Radix Pseudostellariae(Tai-zi-shen)15g,Rhizoma Atractylodis Macrocephalae(Bai-zhu)20g,Radix Cyathulae(Chuan-niu-xi)15g,Radix Saposhnikoviae(Fang-feng)20g,Sappan Wood(Su-mu)20g,Yerbadetajo Herb(Mo-han-lian)20g,Cherokee Rose Fruit(Jin-ying-zi)20g,Herba Leonuri(Yi-mu-cao)30g,Sichuan Lovage Rhizome(Chuan-xiong)20g,Chicken’s Gizzard-skin(Ji-nei-jin)20g,Orange Fruit(Zhi-qiao)20g,Rhizoma Cimicifugae(Sheng-ma)20g,Ovientvine Stem(Qing-feng-teng)30g,Gordon Euryale Seed(Qian-shi)20g,Glossy Privet Fruit(Nv-zhen-zi)20g,Dodder Seed(Tu-si-zi)15g,Chinese Gall(Wu-bei-zi)20g,Chinese Waxgourd Peel(Dong-gua-pi)20g,Poria peel(Fu-ling-pi)30g,Dragon Bone(Long-gu)20g,Oyster shell(Mu-li)25g.These medicines were boiled together with water one dose per day.Take the warm water decoction twice one day after meals in the morning and evening.

Formula analysis:Radix Cyathulae(Chuan-niu-xi),Dodder Seed(Tu-si-zi),Yerbadetajo Herb(Mo-han-lian),and Glossy Privet Fruit(Nv-zhen-zi)were to warm and tonify kidney yang.Radix Astragali(Huang-qi),Radix Pseudostellariae(Tai-zi-shen),Rhizoma Atractylodis Macrocephalae(Bai-zhu),Chicken’s Gizzard-skin(Ji-nei-jin),and Orange Fruit(Zhi-qiao)were used to invigorate spleen and replenish qi.Gordon Euryale Seed(Qian-shi),Chinese Waxgourd Peel(Dong-gua-pi),Poria peel(Fu-ling-pi),andHerba Leonuri(Yi-mu-cao)were used to induce diuresis and alleviate edema.Sappan Wood(Su-mu),Sichuan Lovage Rhizome(Chuan-xiong),and Cherokee Rose Fruit(Jin-ying-zi)were used to promote blood circulation for removing blood stasis.Cherokee Rose Fruit(Jin-ying-zi),Rhizoma Cimicifugae(Sheng-ma),and Chinese Gall(Wu-bei-zi)were used to clear heat,release exterior,dispel wind and constrain the lung.Ovientvine Stem(Qing-feng-teng)was used to expel wind and dredge collaterals.Dragon Bone(Long-gu)and Oyster shell(Mu-li)were used to tranquilize mind with heavy sedatives and balance yin and yang.

As for Western medicine treatment,we adopted strategies to anti-infection(Piperacillin Sodium and Sulbactum Sodium),ease a cough(Budesonide Suspension),promote urination(Compound Dextran and Torasemide),relieve the edema,anti-coagulate(Low-molecular-weight Heparin Calcium and Calcium Gluconate),and decrease hypercholesterolemia(Atorvastatin Calcium Tablets).Enalapril Maleate was used to reduce proteinuria.Tripterygium Glycosides(TGT)was used to dispel wind and remove dampness,and Glutathione Tablets was used to protect liver to reduce side effects of TGT.In addition,to inhibit inflammatory response and control albuminuria loss,Methylprednisolone Sodium Succinate was initiated at a dosage of 80mg once a day,and then was changed to Methylprednisolone Tablets orally after discharge(Table1),meanwhile Calcium was given to prevent osteoporosis and other side effects.

On March 13,the swelling of the patient was significantly catabatic(24hUTP was 2.78mg with 2645mL urine volume).And cough and fatigue were also relieved.And he returned to normal temperatureon March 8(Figure 2).The patient was with purple tongue,slimy yellow tongue fur,deep and fine pulse.At this stage,TCM decoctions were adjusted to give priority to promoting blood circulation,strengthening heat clearing and reducing diuresis and detumescence.Specific prescription was as follows: based on the former one,Dodder Seed(Tu-si-zi),Radix Pseudostellariae(Tai-zi-shen),Chinese Waxgourd Peel(Dong-gua-pi)and Poria peel(Fu-ling-pi)were subtracted,andCortex Moutan(Mu-dan-pi)20g,Radix Scrophulariae(Xuan-shen)20g,Cortex Phellodendri(Huang-bai)20g,Rhizoma Anemarrhenar(Zhi-mu)20g were added.Oral drugs were additionally given to Kunxian Capsule [medicine composition: Kunming Begonia(Kun-ming-shan-hai-tang),Epimedium Herb(Yin-yang-huo),Wolfberry Fruit(Gou-qi-zi),and Dodder Seed(Tu-si-zi)] to tonify kidney,remove wind and dehumidify collaterals,Zhishetongluo Capsule[medicine composition:Hirudo(Shui-zhi),Black-tail Snake(Wu-shao-snake),Radix Astragali(Huang-qi),Salvia Root(Dan-shen),andRhizoma Acori Tatarinowii(Shi-chang-pu)] to replenish qi for activate blood,extinguish wind and unblock collaterals.One week later,Methylprednisolone Sodium Succinate was changed to 60mg/d.

On March 25,puffiness around the body basically disappeared and heavy feeling of lower extremities,cough,expectoration and sore throat were getting improved.Light purple tongue,thin yellow greasy coating,sunken pulse.Based on the therapeutic principles of invigorating spleen and tonifying kidney,clearing heat and activating blood circulation,Sappan Wood(Su-mu)and Cherokee Rose Fruit(Jin-ying-zi)were subtracted from the above prescription,meanwhile Cuttlebone(Hai-piao-xiao)20g,Wingless Cockroach(Tu-bie-chong)20g and Herba Hedyotis(Bai-hua-she-she-cao)20g were added to further strengthen the heat-clearing and activating blood circulation.

On April 2,the patient was discharged from hospital because the condition was stable.The glucocorticoid had been changed to oral tablet with a dose of 40mg QD,and other drugs were prescribed as usual.Reexamination on April 18 showed that the patient still had cough and dizziness.With the decreasing of albuminuria(0.36g/24h,2500mL urine volume),swelling totally vanished and his weight had dropped to 68kg.TC and LDL-C were still high but improved and albumin was on the rise.The overall trend was towards recovery.According to clinical symptoms and relevant lab tests,the TCM decoctions were adjusted as follows: several medicines includingRhizoma Cimicifugae(Sheng-ma),Ovientvine Stem(Qing-feng-teng),Gordon Euryale Seed(Qian-shi),Cortex Phellodendri(Huang-bai)and Cuttlebone(Hai-piao-xiao)were subtracted from the above one andHerba Sedi(Chui-pen-cao)15g andWinged Euonymus Twig(Gui-jian-yu)15g were added.The rest oral medications were the same as before,and Methylprednisolone was adjusted to 28mg per day.

Mother’s father worked as a carpenter. On this particular day, he was building some crates2 for the clothes his church was sending to an orphanage3 in China. On his way home, he reached into his shirt pocket to find his glasses, but they were gone. He remembered putting them there that morning, so he drove back to the church. His search proved fruitless.

On June 22,serum ALB was effectively increased and symptoms improved.The patient was with light purple tongue,thin and white coating,sunken and thin pulse.Methylprednisone Tablet was changed to 24mg,which was taken every other day.The Zhishetongluo Capsule had been discontinued,thus the decoctions had to increase the intensity of promoting blood circulation and removing blood stasis.The total prescriptions were regulated to: Milkvetch Root(Huang-qi)30g,Rhizoma Atractylodis Macrocephalae(Bai-zhu)15g,Radix Cyathulae(Chuan-niu-xi)15g,Chinese Gall(Wu-bei-zi)20g,Chicken’s Gizzard-skin(Ji-nei-jin)20g,Orange Fruit(Zhi-qiao)30,Herba Leonuri(Yi-mu-cao)20g,Chinese Magnoliavine Fruit(Wu-wei-zi)20g,Liquorice Root(Gan-cao)15g,Ovientvine Stem(Qing-feng-teng)30g,Sappan Wood(Su-mu)20g,Rhizoma Polygoni Cuspidati(Hu-zhang)20g,Sichuan Lovage Rhizome(Chuan-xiong)30g,Salvia Root(Dan-shen)30g,Rhizoma Sparganii(San-leng)20g,Rhizoma Curcumae(E-zhu)20g,Yerbadetajo Herb(Mo-han-lian)20g,Plantain Seed(Che-qian-zi)15g,Ramulus Cinnamomi(Gui-zhi)20g,Glossy Privet Fruit(Nv-zhen-zi)20g,Dragon Bone(Long-gu)20g,Oyster shell(Mu-li)25g.

On July 25,TP and ALB were close to normal,urine analysis and liver function tests dropped to normal levels.According to the patient’s condition,Glutathione Tablets were stopped and Zhengqingfengtongning Tablets(main ingredient:Sinomenine Hydrochloride)were taken to dispel wind,remove dampness,reduce swelling,promote blood circulation and unblock collaterals.Methylprednisolone Tablets were shifted to 16mg and taken every other day.

On September 11,all unwell symptoms improved and the condition tends to be stable.Methylprednisolone was reduced to 8mg QOD.Lipid-lowering drugs were stopped because TC and LDL-C within normal range.With the decrease of glucocorticoid dosage,TCM decoction was modified to invigorating spleen and kidney,assisted by promoting blood circulation and removing blood stasis.The prescription was as follows:Radix Astragali(Huang-qi)30g,Fructus Corni(Shan-zhu-yu)15g,Rhizoma Dioscoreae(Shan-yao)15g,Cortex Eucommiae(Du-zhong)20g,Radix Polygoni Multiflori(He-shou-wu)20g,Radix Cyathulae(Chuan-niu-xi)15g,Radix Morindae Officinalis(Ba-ji-tian)15g,Glossy Privet Fruit(Nv-zhen-zi)20g,Fructus Lycii(Gou-qi-zi)20g,Fructus Forsythiae(Lian-qiao)15g,Red Peony Root(Chi-shao)15g,Wingless Cockroach(Tu-bie-chong)20g,Yerbadetajo Herb(Mo-han-lian)20g,Ramulus Cinnamomi(Gui-zhi)20g,Plantain Seed(Che-qian-zi)15g,Herba Lycopi(Ze-lan)20g,Radix Trichosanthis(Tian-hua-fen)20g,Radix Pseudostellariae(Tai-zi-shen)20g.

On October 30,Methylprednisolone Tablets were shifted to 4mg QOD.The laboratory examinations revealed that proteinuria was negative(0.09mg/24h,2050ml).Yet the symptoms of poor sleep at night still existed that decoctions should be modified to promote blood circulation and tranquilize mind.The prescription was as follows:Radix Astragali(Huang-qi)30g,Dodder Seed(Tu-si-zi)15g,Fructus Psoraleae(Bu-gu-zhi)20g,Chinese Gall(Wu-bei-zi)20g,Rhizoma Atractylodis Macrocephalae(Bai-zhu)20g,Radix Saposhnikoviae(Fang-feng)15g,Chicken’s Gizzard-skin(Ji-nei-jin)20g,Orange Fruit(Zhi-qiao)20g,Sappan Wood(Su-mu)20g,Sichuan Lovage Rhizome(Chuan-xiong)20g,Radix Cyathulae(Chuan-niu-xi)15g,Hirudo(Shui-zhi)5g,Herba Leonuri(Yi-mu-cao)20g,Zanthoxyli(Chuan-jiao)20g,Concha Margaritifera(Zhen-zhu-mu)30g,Dragon Bone(Long-gu)20g,Oyster shell(Mu-li)25g.

On December 10,all lab tests were negative and Methylprednisolone tablets were discontinued.As the illness dissolved,appetite increased and his weight had risen to 70kg.As stated in the Chapter 3 of Plain Questions: “the key factor of Yin and Yang is that only when Yang is compact can it strengthen Yin-Essence.The imbalance between Yin and Yang is just like a year that only has spring but no autumn or only has winter but no summer”.Therefore,during the recovery period,attention should be paid to benefiting both Yin and Yang,so as to figure the above formula:Fructus Psoraleae(Bu-gu-zhi),Chicken’s Gizzard-skin(Ji-nei-jin),Sappan Wood(Su-mu),Hirudo(Shui-zhi),Herba Leonuri(Yi-mu-cao),Zanthoxyli(Chuan-jiao)were removed and addedFructus Lycii(Gou-qi-zi)20g,Chinese Magnoliavine Fruit(Wu-wei-zi)15g,Mulberry Fruit(Sang-shen)20g,Glossy Privet Fruit(Nv-zhen-zi)20g,Yerbadetajo Herb(Mo-han-lian)20g,Radix Bupleuri(Chai-hu)20g,Epimedium Herb(Yin-yang-huo)15g,Gordon Euryale Seed(Qian-shi)20g were added.

On January 14,2019,laboratory tests,including routine blood test,urinalysis,liver function,serum creatinine,24hUTP,were within normal levels.The patient’s general clinical manifestations were in order.Decoctions given after four diagnostics of TCM and Huangkui Capsule(essential: Huangshukui flower)were used to clear heat and moisten,detoxify and detumescence to consolidate the goodness.

From March to May 2019,the patient went to outpatient clinic for reexamination on time,and the discomfort symptoms basically disappeared.With the stability of his state,oral medicines were also reduced or discontinued.

Discussion

NS is one of the common refractory diseases in clinic,which has the characteristics of lingering,persistent and recurrent [2].Clinically,NS can be divided into primary and secondary categories.Primary NS is caused by a variety of pathological types of primary glomerulonephritis.The pathogenesis is related to immune response including humoral immunity,cellular immunity,immune mechanism involving inherent cells of kidney,heredity,environment and other factors,among which immune-mediated immune response and inflammatory injury are regarded as the most important pathogenic factors [3].Infection is the most common complication of NS,which is the main fatal cause of Refractory Nephropathy and recurrence of NS [4],of which respiratory infection accounts for 60% ~ 80% as the most frequent type [5].Patients suffering from NS are in low immune function.It has been reported that [6]hypoalbuminemia and immune dysfunction accompanied by NS patients will increase the risk of infection and aggravate the situation.In this case,the patient developed foam urine 3 years ago,but no attention was paid to until the swelling occurred after the onset of exogenous wind chill.This patient is a typical infection-induced NS,which the treatment difficulty is greater than simple NS.The existence of pulmonary infection also greatly affects the therapeutic regimen of NS.There are many problems should be considered,such as glucocorticoid,the first choice drug for NS,what is the initial dose for severe pulmonary infection,then what’s the withdrawal speed,and when to utilize TCM and what’s the focus of decoction adjustment,how to reduce complications,etc.Therefore,looking for a practical and curative treatment scheme which not only slow or prevent further kidney damage but improve the efficacy and quality of life for people suffering NS is important.

To sum up,in terms of treatment,TCM took invigorating spleen and kidney,promoting blood circulation and promoting diuresis as its basic treatment principle.In Western medicine,glucocorticoid and immunosuppressants were common drugs to treat NS,which can quickly control proteinuria.But long-term use of glucocorticoid and immunosuppressants may bring many side effects and complications,such as decreasing body resistance,rebound phenomenon,and increasing treatment difficulty.The course of treatment could be too long to decrease patient’s compliance if only used TCM.Surprisingly,the combination of traditional Chinese and modern Western medicine could reduce their deficiency.That is to say,the treatment based on syndrome differentiation of TCM,supplemented by glucocorticoid and/or immunosuppressive agent could make a different.This combination therapy scheme will greatly shorten the use time and dosage of glucocorticoids,which not only can control macroalbuminuria and high edema in a short time,but also antagonize yin deficiency,internal heat or damp-heat symptoms in the body caused by long-term use of high-dose glucocorticoids,and reduce adverse reactions such as hormone dependence or disease rebound caused by the use of hormone and immunosuppressive agents.At the later stage of the disease,Chinese medicines were given to benefit the congenital and acquired foundation,strengthen physique,consolidate the improvement and reduce recurrence rate.

Glucocorticoid,as an exogenous hormone,has always been regarded as a pungent,dry,sweet and warm product from the perspective of TCM.The longer it is used,the stronger the toxic and side effects it feeds back to the body,including moon-face,buffalo hump,central obesity,dysphoria,insomnia,peptic ulcer and other symptoms,which are not conducive to the recovery of disease.Many reports believe that [7,8]glucocorticoid with the properties of pungent and warm often injures yin and yang and aggravate kidney deficiency when treating Chronic Kidney Disease.It will help heat to generate dryness,consume qi and injure yin.It will cause blood stasis and aggravate blood stasis.Furthermore,the time control of initial glucocorticoids usage,withdrawal and maintenance is flexible and empirical.When the glucocorticoid is used in large doses,it is usually manifested as yin deficiency and fire hyperactivity syndrome.When the glucocorticoid is used in small doses,it is mostly manifested as spleen and kidney qi deficiency syndrome.When the glucocorticoid is used in maintenance amount,it is mostly manifested as spleen and kidney yang deficiency or yin and yang deficiency syndrome.However,these rules are not static but should be analyzed in detail for specific problems.In this case,low-dose,short-course glucocorticoid was adopted.The initial dosage of methylprednisolone of the patient was 80mg/d,which conforms to 1 mg/(kg·d)[2],and this dosage was maintained for 2 weeks.From the 14th day onwards,it was altered to 60mg/d and lasted for 1 week.Glucocorticoid was adjusted to 40 mg/d from the 21st day.On April 18,it was changed to 28mg/d,and then 4mg of glucocorticoid was withdrawn every 2 weeks.Up to June 3,the dosage was 16mg.Starting from June 22,the glucocorticoid administration was adjusted to 24mg once every other day.On July 25,it was altered to 16mg and taken every next day(the glucocorticoid reduction was slightly larger this time because all the lab findings at this stage were close to normal and the patient was in stabilized condition).After that,4mg was withdrawn every month until the drug was completely discontinued.In this report,the use of glucocorticoid was less than that of conventional scheme only using Western medicine,and the withdrawal speed in theearly stage was fast,especially in the first month of treatment,then slowed down and regularity.The drug reduction speed was initially based on “week” and then based on “month”.Administration time was changed from once every day to once every other day.The glucocorticoid was only taken for 9 months(March 2018 to December 2018)in the whole course,far shorter than the regular time of at least 12 months.And there were no flares or by-effects with the assistance of TCM.

In TCM,NS belongs to the categories of “Edema(Shuizhong)”,“Vacuity Taxation(Xu-lao)”,“Urinary Turbidity(Niaozhuo)”,“Urinary Blockage(Longbi)”or even "Anuria and Vomiting(Guange)”.NS has various clinical manifestations,and edema is the most common clinical presentation.The metabolism of water in human body mainly depends on the circulation of lung,the opening and closing of kidney and the transference of spleen.The pathogenesis of NS is the deficiency of lung,spleen and kidney.Meanwhile,the imbalanced relationship among water,qi and blood is the key factor.The disharmony among water,qi and blood results in the accumulation of dampness,heat and blood stasis in the body,which is manifested as root vacuity and tip repletion,while deficiency and blood stasis run throughout the disease[9].Hence,TCM treatment is based on the principles of invigorating spleen and kidney,promoting blood circulation and removing blood stasis,clearing heat and promoting diuresis.Besides the four diagnostics of TCM in this case,it is also necessary to judge and analyze the dosage and time of using glucocorticoid,and reasonably combine TCM to achieve the best therapeutic result.

At the initial stage of admission,the patient had general swelling especially in both lower extremities,accompanied by massive proteinuria(14.28g/d))and hypoproteinemia(23g/L).“Synopsis of the Golden Chamber” has a saying: “For those patients with edema swelling below the waist should be cured by promoting urination,while swelling above the waist should be cured by sweating.” Edema is yin evil,and its moving is downward naturally.The waist of the human body is subordinate to yin,and yin is in the yin position,resulting in swelling below the waist.Therefore,his TCM treatment was mainly to diuresis and detumescenceto made “water qi” discharge from urine and also took into account tonifying spleen and kidney,activating blood stasis,which the later one should run through the he whole therapy process.Because the blood of NS is mostly in hypercoagulable and high-fat state,and microthrombosis is easy to form,which seriously affects the microcirculation of kidney tissue and is not conducive to the excretion of metabolic products.Glucocorticoid,as a pungent and dry product,further fry and scorch blood and accelerate the formation of blood stasis.There is a saying in TCM that “chronic diseases easily enter collaterals and resulting in blood stasis”.Blood stasis,as an important pathological product and pathogenic

factor of NS,should be paid attention to.It is not difficult to find that there are blood-activating herbs in the prescriptions before and after treatment,which can promote blood circulation,remove blood stasis and unblock collaterals,promote circulation of renal microvasculature and recovery of renal function,resist coagulation and reduce blood lipid as well.After effective diuresis by combining Chinese and Western medicine,the manifestation of edema in the whole body was obviously relieved,thus reducing the use of diuretic and detumescence herbs and increasing the ones to promote blood circulation.

At the same time,considering the administration time and dosage of glucocorticoid,the patient appeared slight yin deficiency and transferred into heat with slightly yellow and greasy tongue coating that herbs to clear heat and eliminate dampness should be increased.When the disease was stable without flares and the lab findings were within normal levels,invigorating spleen and kidney should be acted as crucial point with TCM treatment during stable period,so as to tonify the innate and acquired foundation.In the whole therapeutic procedure,one prescription must not be used to the end,which is forbidden by TCM doctors.Only when we treat it according to time,place and people can we make Chinese medicine play its role.

Moreover,Kunxian Capsule,TGT and Zhengqingfengtongning Tablets,as TCM immunosuppressants,play an indispensable role in the therapeutic process of NS,which are quite different from Western medicine immunosuppressants such as Cyclophosphamide and Cyclosporine.Kunxian Capsule has the function of expelling wind and dampness,warming collateral and dispelling cold,nourishing liver and kidney,and relieving pain.Its main ingredient,Kunming begonia(Kunmingshanhaitang),can antagonize inflammatory mediators,which inhibit the secretion of T cells,macrophages,and vascular endothelial cells.Having a“hormone-like” effect,but no adverse effects of hormone so compared with high-dose glucocorticoid and Cyclophosphamide,it has great advantages [10].TGT has strong anti-inflammatory and immunoregulatory effects,especially on proteinuria control.However,it can cause liver damage,so liver-protecting drugs should be added,and regularly liver enzymes test is needed [10].Sinomenine Hydrochloride,the main component of Zhengqingfengtongning Tablet,is extracted from the herb Ovientvine Stem(Qingfengteng),resulting in analgesic,anti-inflammatory and controlling proteinuria,which has inhibitory effects on non-specific immunity,humoral immunity and cellular immunity [11].These three groups of TCM immunosuppressants,according to the patient’s condition and medications characteristics,were respectively applied to different stages of therapy,used in combination or alone,and have a great influence on the rehabilitation.

This is a typical case of NS accompanied by severe pulmonary infection with significant proteinuria treated by TCM and low-dose glucocorticoid.By taking a small dose of glucocorticoid,combined with long-term treatment of TCM decoction,the disease was effectively controlled.After one week hospitalization,the presentation of systemic edema basically faded and proteinuria was significantly reduced.At the 7th month of cure,24hUTP reached to normal level and other lab tests were nearly negative.At the 9th month,all lab findings were kept within the normal range,including full-blood count,urinalysis,liver tests,electrolytes and kidney tests,during which no discomfort was found.The relevant reports since the follow-up all were negative(Table 2 and Figure 3).The above good rehabilitation result is largely attributed to the patient's good compliance and the appropriate treatment plan.

TCM has gone through thousands of years in history.Through continuous exploration and application,connected with modern science and technology,human beings have continuously summarized,innovated and developed it.TCM,with its remarkable curative effect and unique thoughts of therapy based on syndrome differentiation,will provide new therapeutic schemes and ideas for nephropathy or other refractory diseases.