Comparative Study of Efficacy of Kutaja Beeja Churna and Ayurvedic Herbal Compound in the Management of Mutrashmari (Urolithiasis)- A Research Protocol

1. PG Scholar, Department of Shalya Tantra, Mahatma Gandhi Ayurved College Hospital and Research Centre, Wardha, Maharashtra, India. 2. Associate Professor, Department of Shalya Tantra, Mahatma Gandhi Ayurved College Hospital and Research Centre, Wardha, Maharashtra, India.

Abstract

Introduction: Acharya Sushruta, the father of surgery has included Ashmari in Astamahagada due to its fatal nature. “Ashman” the Sanskrit word, literally means “structure resembling stone”. While the word ‘Ari' means ‘enemy,' so it refers to a sickness in which stones grow and inflict intense pain, as if caused by an adversary. Mutrashmari can be associated with Urolithiasis which is the third most common affliction of the urinary tract. Acharya Sushruta has described medicinal treatment in the initial stage of the disease and advised that surgery to be done only on failure of conservative treatment and when death becomes inevitable if not operated. In Yogaratnakar, Ashmari chikitsa, Kutaja is described to be more effective in the treatment of Mutrashmari.

Need of study: In modern medicine, the treatment of urinary stones is non surgical as well as surgical interventions but both have some limitations and also stone formation reoccurs after removal. There is a need for safe, cost effective and simple method of management of urolithiasis which is curative as well as preventive.

Aim: Comparative assessment of efficacy of Kutaja Beeja Churna and Ayurvedic Herbal Compound in the management of Mutrashmari (Urolithiasis).

Materials and Methods: A randomised control trial (single blind parallel) with 1:1 ratio on 2 groups and will be conducted in Mahatma Gandhi Ayurved College Hospital and Research Centre Salod (Hi) Wardha. Expected duration of the study is one and half year (February 2022 - August 2023). Approval from the Institutional Ethical Committee has been taken and for this trial the registration number is CTRI/2021/09/036297. For statistical analysis Wilcoxon signed-rank test, Mann Whitney U test, Student’s t-test and the Statistical Package for the Social Sciences (SPSS) software will be used in the study. After doing drug analysis, a total of 60 patients fulfilling the inclusion criteria will be selected and distributed in two groups having 30 each. In group A, Kutaja Beeja Churna and in group B, Ayurvedic Herbal Compound will be given twice a day for 45 days. Assessment will be done on day 15, 30 and 45 and after the intervention; follow-up will be taken on days 60 and 90. Results will be drawn from the observations of subjective parameters like pain and dysuria and objective parameters like size of the stone, site of the stone and haematuria.

Ashtamahagad, Calculus, Holarrhena antidysentrica, Urinary stones

Ashmari refers to a sickness in which stones formation occurs and which causes intense pain, as if caused by an enemy. In our Ayurvedic classics and vedic literature lot of references about Ashmari are present. The earliest reference available is in Atharvaveda (1^st khanda, 3^rd sukta, 6-9 shlokas). Charaka has described it under a type of Mutraghata (1) where as Acharya Sushruta, the father of surgery has included Ashmari in Astamahagada (2) due to its fatal nature and described in detail about Mutrashmari in a separate chapter with its aetiology, classifications, symptomatology, pathology, complications(3) and management (4). Acharya Sushruta described aetiopathogenesis of ashmari as the person one who does not follows Shodhana treatment and who is Apathyakaari (uses unwholesome items), Shlesma Dosha gets aggravated, and saturates in the urine. This saturated urine (Shleshma Yukta Mutra) is the material (cementary substance) which causes urinary stone formation (3).

Ashmari is invariably Tridoshajanya, however, a classification of Ashmari is made based on the predominance of dosha. Ashmari is classified into four types - Vataja, Pittaja, Sleshmaja and Shukraja Ashmari (3). Acharya Sushruta has described medicinal treatment in the early stage of the disease and advised that surgery to be done only on failure of conservative treatment and when death becomes inevitable if not operated. Surgery is indicated along with a note of caution regarding its complication and doubt of success (4).

Urolithiasis means stone in urinary system whether in kidneys, ureters, bladder or urethra. Urolithiasis is the most painful and common disease of the urinary system. After Urinary Tract Infection (UTI) and Benign Prostatic Hyperplasia (BPH), it is the third most common disease of the urinary tract (5). About 15% of men and 5% of women develop renal calculi at some stage. If one has developed renal stones in the past, is likely to have a 70% chance of formation of new stones in the future (6). In India, one out of thousand people needs hospitalisation due to renal stone disease (7). Males are affected three times as frequently as females. The peak incidence of stones occurs between the ages of 20-50 years. The major aetiological factors are inadequate fluid intake, western diet, excessive sweating due to hot climate, high protein diet, meat, calcium rich diet, and sedentary occupation predispose to stones compared with manual workers (8). More common in whites than in black. It is rare in children (9).

In modern medicine, the treatment modalities of urinary stones depend upon size, position of calculi etc. Non surgical management includes watchful waiting and flush therapy, which is time consuming, medical expulsive therapy with calcium- channel blockers or alpha-antagonists, Extracorporeal Shock Wave Lithotripsy (ESWL) and Dormia basket procedure. Medications like Tamsulosin causes higher rates of headache, dizziness, abnormal ejaculation and postural hypertension (10). Surgical intervention includes advanced techniques like Ureteroscopy, Percutaneous Nephrolithotomy (PCNL), Partial Nephrectomy, Nephrolithotomy, Pyelolithotomy, Nephrectomy, Nephrostomy, etc. All these are expensive and invasive therapies; hence needs hospitalisation which is exhausting to patients as well as relatives.

These therapies, however, are therapeutic for urolithiasis, but they cannot prevent the pathophysiology that leads to the production of stones. As a result, stone recurrence after removal has become a typical occurrence. Keeping in view of the limitations in the treatment modalities presently available, there is a need for safe, cost-effective and simple method of management of urolithiasis which is curative as well as preventive. In Ayurveda various churna, ghruta, kshara, kashaya, ksheera and uttarabasti are mentioned by Acharyas to treat different types of Ashmari. In Yogaratnakar and Bhavaprakash, Kutaja is mentioned in Ashmari Chikitsa as an effective treatment for both Sarkara and Ashmari (11).

Holarrhena antidysenterica, which is commonly known as Kutaja, is found in subtropical and tropical regions of Africa and Asia. It is abundant in India, especially in the Himalayan region. It is categorised as a deciduous, laticiferous shrub or a small tree, which attains a height up to 13 m and a girth of 1.1 m with a clear bole of 3-7 m. Its seeds are 8 mm long or more, linear oblong and are known as Indrajava (12).

As multiple factors are involved in the pathogenesis of urolithias is and therefore management demands multiple targets, such as antioxidant, antispasmodic, anti inflammatory activities. Holarrhena antidysenterica contains ergostenol, conessine, kurchicine, holarrhenine, tannin and resin and has been reported to possess antibacterial, antimutagenic, immunomodulatory, diuretic and antispasmodic properties. In-vitro and In-vivo study conducted by Khan A et al., also shows antiurolithic activity of Holarrhena antidysenterica (13).

The Ayurvedic herbal compound that we are using as a standard drug is a readily available drug in market. As the compound is from a reputed drug manufacturing company therefore name of the drug has not been mentioned here to avoid any conflict of interest. However composition of each tablet along with concentration is mentioned here. Each tablet of this compound is of approx. 500 mg having extracts of Shilapuspa (Didymocarpus pedicellata) 130 mg, Pasanabheda (Saxifraga lingulata) 98 mg, Manjistha (Rubia cordifolia) 32 mg, Nagarmusta (Cyperus scariosus) 32 mg, Apamarga (Achyranthes aspera) 32 mg, Gojiha (Onosma bracteatum) 32 mg, Sahadevi (Vernonia cinerea) 32 mg and powders of Hajrul yahood bhasma 32 mg, Shilajeet 26 mg processed in Vanatulsi (Ocimum basilicum), Gokshura (Tribulus terrestris), Lajjalu (mimosa pudica), Kulattha (Dolichos biflorus) Balam (Pavonia odorata), Jaratoota (Equisetum arvense) and Shaka seed (Tectona grandis). Preservatives like Sodium Methylparaben and Sodium Propylparaben is added to it.

The Ayurvedic Herbal compound has been frequently used in practice as a preferred ayurvedic remedy for urolithiasis. As it contains many herbo-mineral drugs, it is very costly and can’t be a drug of choice for all classes of society. So, there is a need for safe, cost-effective and simple method of management of urolithiasis which is curative as well as preventive. Kutaja is economically viable and its seeds have tridoshaghana effect. Hence the study is planned to see efficacy of Kutaja Beeja Churna in management of Mutrashmari.

Objectives

i. To study the efficacy of Kutaja Beeja Churna on subjective and objective parameters in the management of Mutrashmari (Urolithiasis).
ii. To study the efficacy of Ayurvedic Herbal Compound on subjective and objective parameters in the management of Mutrashmari (Urolithiasis).
iii. To compare the efficacy of Kutaja Beeja Churna and Ayurvedic Herbal Compound on subjective and objective parameters in the management of Mutrashmari (Urolithiasis)

Case definition: Mutrashmari- patients with classical features namely Nabhi basti sevni mehaneshu anaytam asmina mehati vedana, mutra dhara sanga, sarudhirmutrata, mutravikiranam, sasiktam (unilateral or bilateral pain in the renal angle, pain in lumbar region, radiating pain from loin to groin, pain in scrotum and inner aspect of thigh, dysuria, haematuria) and presence of calculi confirmed by Ultrasonogram (USG) of abdomen and pelvis will be selected for the study.

Research Question: Whether Kutaja Beeja Churna is equally or more efficacious than Ayurvedic Herbal Compound in the management of Mutrashmari (Urolithiasis)?

Null Hypothesis (H0): Kutaja Beeja Churna is not efficacious as Ayurvedic Herbal Compound in the management of Mutrashmari (Urolithiasis).

Alternative Hypothesis

(H1): Kutaja Beeja Churna is more efficacious than Ayurvedic Herbal Compound in the management of Mutrashmari (Urolithiasis).

(H2): Kutaja Beeja Churna is equally efficacious as Ayurvedic Herbal Compound in the management of Mutrashmari (Urolithiasis).

Material and Methods

A randomised control trial (parallel design) with allocation ratio 1:1 in two groups. Sample size of 60 individuals, with 30 each in control and trial group was calculated by formula: n1=kn2, n2=(z?2/=z?) 2x2 (1=1k/) (?E-?C-?)2. The sampling technique will be random sampling by computerised table method. The study will be conducted in Mahatma Gandhi Ayurved College Hospital and Research Centre Wardha, Maharashtra, India. Expected duration of the study is one and half year (February 2022-August 2023). Approval from the Institutional Ethical Committee (IEC) has been taken and the reference number is MGACHRC/IEC/January-2022/435. The trial is registered under CTRI and registration number is CTRI/2021/09/036297. Informed consent will be taken before starting the trial. Gantt chart for study protocol has been given in (Table/Fig 1).

Inclusion criteria: Patients from age group of 20 to 50 years, irrespective of gender, occupation and economic status complaining of Nabhi basti sevni mehaneshu anaytam asmina mehati vedana (unilateral or bilateral pain in the renal angle, pain in lumbar region and radiating pain from loin to groin, pain in scrotum and inner aspect of thigh or pain in atleast any one or more of above said sites), with or without dysuria (mutra dhara sanga), with or without micro haematuria (sarudhirmutrata) and with solitary or multiple urinary calculi present anywhere in urinary tract measuring between 5 to 9 mm size confirmed by USG abdomen and pelvis.

Exclusion criteria: Patients suffering from chronic diseases such as diabetes mellitus, hypertension, tuberculosis, Human Immunodeficiency Virus (HIV) positive, hepatitis B positive, reported cases of malignancy, ulcerative colitis, Crohn’s disease or have disorders like renal failure, massive hydronephrosis Cushing’s syndrome, polycystic kidney, urethral stricture, meatal stenosis, bladder neck contracture. Also patients who are Coronavirus Disease-2019 (COVID-19) positive and pregnant women will be excluded.

Criteria for discontinuing or amending the interventions: The patient will be withdrawn from the study if any event, drug susceptibility characteristics or some other illness or condition occurs. The patient will be given free treatment till the condition subsides.

Drug collection/ authentication and details of drug preparation: The raw material will be collected from local market and the drugs will be identified and authenticated by Department of Dravayguna of MGACH & RC, Salod(H), Wardha. Kutaja Beeja Churna will be prepared in Dattatraya Rasa Shala of MGACH & RC under supervision of subject experts by following the guidelines of Churna Kalpana mentioned in Bhaisjya Kalpana (14).

Ayurvedic herbal compound that we are using is a readily available drug in medical stores. We are not making this compound. It is a fixed dose combination of several herbs which is already available in market.

Primary outcomes: Primary objective is to study the efficacy of Kutaja Beeja Churna on subjective and objective parameters in the management of Mutrashmari (Urolithiasis). Possible primary outcome is that Kutaja Beeja Churna will reduce pain, dysuria, haematuria and at the same time it will defragment the calculus and make it easier to pass through urinary tract.

Secondary outcomes: Secondary objective is to compare the efficacy of Kutaja Beeja Churna and Ayurvedic Herbal Compound on subjective and objective parameters in the management of Mutrashmari (Urolithiasis). As Kutaja is easily available all over India hence this study will contribute to cost-effective, safe, readily available, simple preparation and a good remedy for managing Mutrashmari.

Schedule of enrollment, interventions: Medications will be given daily two times a day for 45 days. Assessment will be done on day 15, 30, 45 and follow-up after intervention will be taken on day 60 and 90.

Implementation: Principal Investigator will register subject and blinding will be ensured by the fact that participants will be deliberately kept ignorant of either the group to which they have been assigned. Two groups each with minimum of 30 patients will be included (Table/Fig 2), (Table/Fig 3).

Assessment criteria

a. Subjective parameters:
1. Pain
2. Dysuria

Objective Parameters:

1. Size of the stone (reduction in %) (by USG)
2. Site of the stone (location confirmed by USG)
3 Haematuria (no of Red Blood Cells (RBCS)/Hpf)

Gradation of Symptoms

Subjective Parameters:

i. Pain- Pain of any degree and type, occurring at any sites of urinary system (15).
ii. Dysuria- Will be assessed by history of pain and radiation during micturition (15).
Objective Parameters:
i) Haematuria - As observed in microscopic urine examination.
ii) Descent of the calculi - As seen in USG abdomen and pelvis.
iii) Size of the calculi - Change in size of calculi as seen in USG abdomen and pelvis.

Data management: Principal investigator will do coding of data.

Consent or assent: The written consent will be taken from the patient before starting the study. During the study the confidentiality of each patient will be maintained.

Dissemination policy: The data will be disseminated by paper publication. Authorship eligibility guidelines and any intended use of professional writers

Informed consent materials: With all the information model consent form and other related documentation will be given to participants.

Statistical Analysis

For statistical analysis, the software we are using is SPSS. The level of significance is at 95% and the tests for significance are Mann-Whitney U test, Wilcoxon signed-rank test, Student’s t-test which will be applied on the observations of subjective parameters like pain and dysuria and objective parameters like size of the stone, site of the stone and haematuria.

Discussion

Various types of ashmari are Vataja, Pittaja, Sleshmaja and Shukraja Ashmari. In Vataja Ashmari, the clinical features are severe pain during micturition, clenches his teeth, squeezes the umbilical region, touches his scrotal region, touches his perineal regions, shouts loudly, feels burning sensation all over the body, passes vata, mootra and purisha with high difficulty. While the Vataja Ashmari will have shyava varna, vishama edges and resembles hard studded with thorns like Kadamba Pushpa. In Pittaja Ashmari, the clinical features Dooshyana, chooshana, dahana, Pachana and symptoms of Ushnavata will be seen. (Burning sensation and inflammatory changes in urinary tract). The Pittajashmari will have Rakta Varna or Peetavarna or Krishnavarna or Madhuvarna and resembles ballataka asthi. In Sleshmaja Ashmari, clinical features like Daalyana, bhedana, nisthoda, basti gurutha & shitata (Cutting, pricking, and incising pain in the bladder area, as well as heaviness and a cold sensation.) The Kaphaja Ashmari will have shwetha or Madhukapushpa varna and resembles kukkutanda. In Shukraja Ashmari, Sukrashmari (spermolith) develops in the adults giving rise to mootrakrichra (difficulty in micturition), pain in the basti pradesha, vrushanayoho Shopha (swelling in the testicular/scrotal region). It also has the unique property of being able to be crushed into powder under pressure. Children won’t suffer from Shukrashmari as shukra is not secreted and hence there is no formation of Ashmari in relation to Shukra in Basti (3).

Various types of stones are found in urinary tract based on their composition. These are oxalate, phosphate, uric acid, cystine and some rare stones also. Oxalate stones typically form in the pelvis or calices and are prone to passing through the ureter. About 60-70% of overall calculi are made up of them. The altered blood is deposited on the edge of stones and stone is rigid, granular like mulberries, with pointed edges. Phosphate stones form in the bladder and grow quickly in an alkaline urine environment. They have a smooth texture, a grayish white appearance, and a chalky texture. Phosphatic calculus, often known as staghorn calculus, is radio opaque. These stones are generally made up of triple phosphate and can frequently develop to an enormous size. Stones of uric acid form in the urinary bladder or the renal pelvis are firm, finely granulated, round to elliptical in shape, and yellowish to reddish brown in colour. Urate stones are usually radio-opaque due to the presence of calcium oxalate crystals. Cystine stones are a rare occurrence (0.4%) that results from a metabolic error. These are waxy, rigid, and have a smooth surface. They are pink or yellow in colour. Usually numerous and located in the renal pelvis and calices. These, too, have a proclivity to return after being surgically removed. Calcium carbonate, xanthine, silicate calculi, ammonium acid, matrix calculi, indigo, urate calculi, and bacteria, in rare cases, can produce microscopic soft concretions (9).

Urolithiasis is managed by various modern surgical and medical treatments. These therapies, however, are therapeutic for urolithiasis, but they cannot prevent the pathophysiology that leads to the production of stones. As a result, stone recurrence after removal has become a typical occurrence. In Ayurveda various churna, ghruta, kshara, kashaya, ksheera and uttarabasti are mentioned by Acharyas to treat different types of Ashmari. In Yogaratnakar and Bhavaprakash, Kutaja is mentioned in Ashmari Chikitsa as an effective treatment for both Sarkara and Ashmari. Kutaja has tikta, kshaya rasa; sheeta virya; katu vipaka and is kapha pitta samaka while its seeds are tridoshaghna. Also there is only one animal study done on Holarrhena antidysenterica outside India whose findings suggest that Holarrhena antidysentrica's preventive effect in urolithiasis is mediated through multiple pathways, including inhibition of CaOx crystal aggregation, antioxidant, and epithelial cell protective effects (13). Hence the study is planned to see efficacy of Kutaja Beeja Churna in management of Mutrashmari. Since Kutaja is available everywhere in India, this research will help provide simple, safe, affordable and cost-effective preparation and good remedies for managing Mutrashmari. Therefore this work will serve as a torchbearer in further similar research works. If the proposed study yields a favourable result, that is, if the signs and symptoms of Mutrashmari are eased along with the passing of calculi, it will set a benchmark and provide the best parallel method for the treatment of Mutrashmari (Urolithiasis).

Acknowledgement

The authors recognise the invaluable assistance provided by the scholars whose articles are mentioned and referenced in this manuscript. The authors are also appreciative to the authors, editors, and publishers of all the papers, journals, and books that were used to review and debate the literature for this work.

DOI and Others

DOI: 10.7860/JCDR/2022/57763.16875

Date of Submission: May 13, 2022
Date of Peer Review: Jun 23, 2022
Date of Acceptance: Aug 09, 2022
Date of Publishing: Sep 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: May 16, 2022
• Manual Googling: Aug 08, 2022
• iThenticate Software: Aug 26, 2022 (14%)

ETYMOLOGY: Author Origin