1. INTRODUCTION

1.1 Urolithiasis is one of the most common urological disease with a significant worldwide prevalence of around 5% to 10%¹.

1.2 A large number of people are suffering from Urolithiasis all over the world².

1.3 It is most common between third to sixth decades of life¹.

1.4 Men are more commonly affected than women and in India around 12% of the total population is expected to have Urolithiasis³.

1.5 The risk for Nephrolithiasis exceeds 6% to 12% in the general population, and the prevalence and incidence of kidney stone disease are increasing all over the world and differ in terms of sex, race and environment^4,5.

1.6 Concurrent with the westernization of Asian culture, nephrolithiasis has increased recently in Asian countries⁶.

1.7 Renal calculi are polycrystalline aggregates containing crystal and organic matrix components. The common stones are calcium oxalate, calcium phosphate, uric acid, struvite and cystine stones.

1.8 Due to advanced diagnostic and treatment modalities, nephrolithiasis were treated by many non-invasive techniques like Extra Corporeal Shock Wave Lithotripsy (ESWL), Ureterorenoscopy (URS), Retrograde Intra Renal Surgery (RIRS) and by minimal invasive procedures like Per Cutaneous Nephrolithotomy (PCNL), having excellent results with low morbidity.

1.9 Recurrent stone formation is a common problem with all types of stones, therefore preventive measures are an important and an integral part of the patient care with nephrolithiasis.

1.10 Etiopathogenesis of nephrolithiasis is multifactorial. However, some studies have indicated a significant association between Nephrolithiasis and Syndrome X^7,8.

1.11 Metabolic syndrome or Syndrome X is a worldwide, metabolic disorder, with increasing prevalence year by year.

1.12 It is well known as a constellation of obesity, elevated fasting glucose, elevated triglycerides, lowered high density lipoprotein cholesterol (HDL-C) and elevated blood pressure within an individual⁹.

1.13 Reaven et al coined the termed ‘Syndrome X’ for this constellation of various metabolic derangements including glucose intolerance, hypertension, increased Low Density Lipoprotein Cholesterol (LDL-C), increased Very Low Density Lipoprotein (VLDL), increased triglycerides, and reduced High Density Lipoprotein Cholesterol(HDL-C) along with insulin resistance being the basic pathophysiologic cause^10,11.

1.14 Studies have focused on the search for a pathophysiological association between the different components of metabolic syndrome (Hypertension, Obesity, Diabetes and Dyslipidemia) and nephrolithiasis^5,7,8.

1.15 The exact relationship between Nephrolithiasis and Syndrome X remains controversial, but various pathophysiological mechanisms proposed are: abnormalities of renal calcium metabolism behind the link between hypertension and nephrolithiasis, decreasing urinary pH and defective excretion of ammonia related to obesity and insulin resistance, increased urinary calcium and excretion of uric acid, decreased excretion of urinary citrate which is an inhibitor of nephrolithiasis and renal lipotoxicity due to excess triglyceride levels⁹.

1.16 Metabolic syndrome has also been shown to be associated with certain urological conditions such as male hypogonadism, overactive bladder, erectile dysfunction although data on these conditions are not definite. Fasting plasma insulin, has been linked to Benign Prostatic Hyperplasia and an aggressive and lethal prostate carcinoma¹².

1.17 Nephrolithiasis not only causes acute illness to patients who are suffering pain, but also many medical expenditures. Thus if an association between Nephrolithiasis and Syndrome X is verified then both of them can be prevented by controlling the risk factors, more commonly in a healthy population.

1.18 Therefore this study is conducted to evaluate and investigate an association between patients with Nephrolithiasis and Syndrome X, and to compare with patients without nephrolithiasis at our institute.

2. AIMS AND OBJECTIVES

2.1 AIM

To evaluate the association between Nephrolithiasis and Syndrome X and between each Syndrome X components with Nephrolithiasis

2.2 OBJECTIVES

2.21 To evaluate the association between Nephrolithiasis and Syndrome X.

2.22 To evaluate the relationship between each Syndrome X components with Nephrolithiasis.

2.23To evaluate the incidence of Syndrome X in patients without Nephrolithiasis.

2.24 To evaluate the presence of most common type of renal calculi in patients with both Syndrome X and Nephrolithiasis.

4. MATERIALS AND METHODOLOGY

4.1 TYPE OF STUDY: An Observational Case Control study

4.2 PLACE OF STUDY: Department of Urology at Bhaktivedanta Hospital and Research Institute, Mira Road.

4.3 PERIOD OF STUDY: 2 years

4.4 Institute Ethics Committee approvals and consent will be obtained before the start of the study.

4.5 SAMPLE SIZE:2 groups- A and B

Sample size was calculated using formula:

Nephrolithiasis group: 128.84 + 16.95, n₁= 639

Non-Nephrolithiasis group: 124.46 + 16.56, n₂= 3154

Confidence level= 95%, Z_α= 1.96

Power= 85%, Z_β= 1.04

Absolute precision= E= 5%

Where;

n=sample size

Z = Level of significance

SD = Standard deviation

E= Absolute error

n = 2 (Z_α + Z_β) ² SD²

                   E²

Where SD= √(n₁-1)S₁² + (n₂-1)S₂²

√ n_{1 +} n₂ – 2

=16.63

n= 2(1.96+1.04)² (16.63)²= 199.12= ~200 cases in each group

                      5²

=200cases in each Group A and Group B respectively

Total sample size is 400 cases.

INCLUSION CRITERIA

CASES:

1.     Patients with unilateral or bilateral renal calculi.

2.     Patients giving consent for taking part in the study.

3.     Patients above 18 years of age and of either gender.

CONTROLS:

1.     Patients without renal calculus.

2.     Patients giving consent for taking part in the study.

3.     Patients above 18 years of age and of either gender.

EXCLUSION CRITERIA

CASES:

1.     Acute and Chronic kidney injury patients.

2.     Patients with Congenital urinary tract anomalies.

3.     Patients with complicated calculus diseases like Pyelonephritis, Pyonephrosis, Perinephric abscess and renal abscess.

4.     Pregnant females.

5.     Patients on steroid treatment.

6.     Patients with malignancy.

7.     Patients with gout and gouty arthritic manifestations.

8.     Patients who do not consent to participate in the study.

CONTROLS:

1.     Patients with past history of renal calculi.

2.     Acute and Chronic kidney injury patients.

3.     Patients with Congenital urinary tract anomalies.

4.     Patients with complicated calculus diseases like Pyelonephritis, Pyonephrosis, Perinephric abscess and renal abscess.

5.     Pregnant females.

6.     Patients on steroid treatment.

7.     Patients with malignancy.

8.     Patients with gout and gouty arthritic manifestations.

9.     Patients who do not consent to participate in the study.

4.6 STUDY MEHTODOLOGY:

This Observational case control study was conducted under the Department of Urology at Bhaktivedanta Hospital and Research Institute, Mira Road. Prior approval of Institutional Ethics Committee was taken before start of the study. The details of the study was explained to case and control patients. A written signed informed consent was taken from all the patients prior to their enrolment in the study.Patients were evaluated and the details obtained were recorded in the case record form. Data analysis was done with the collected details prospectively.

All the case and control patients were subjected to Ultrasound examination of both the kidneys. Nephrolithiasis was diagnosed by the presence of hyperechoic focus in the pelvi-calyceal system of the kidney and by casting a posterior acoustic shadow. Patients with Nephrolithiasis were included in Group A (Cases) and patients without Nephrolithiasis were included in Group B (Controls). Groups A and B undergone evaluation for the presence of Syndrome X. Both the groups underwent measurement of:

1.     Waist circumference

2.     Systolic and Diastolic Blood pressure

3.     Fasting blood sugar

4.     Serum HDL cholesterol

5.     Serum Triglycerides

METHODODLOGY FOR EVALUATION OF NEPHROLITHIASIS:

1.     ULTRASONOGRAPHY:

Both the Group A and B patients underwent Ultrasonography using Voluson S8 machine with 5MHz probe. The presence of renal calculi was defined by a hyperechoic focus in the Pelvi-calyceal system and posterior acoustic shadowing.

METHODODLOGY FOR EVALUATION OF EACH SYNDROME X COMPONENTS:

1.     WAIST CIRCUMFERENCE:

Waist circumference was measured using a plastic tape. The measurement was taken with the patients in a relaxed state and standing position with both feet together measured at midpoint of lowermost border of 12^th rib and the upper border of iliac crest at the end of expiration.

2.     BLOOD PRESSURE:

Systolic and Diastolic Blood pressure was measured using Diamond Deluxe sphygmomanometer. Blood pressure was recorded with the patients in sitting posture. Two readings with five minutes apart and their average was taken as the final reading.

3.     BIOCHEMICAL INVESTIGATIONS (Fasting blood sugar, Serum HDL cholesterol, Serum triglycerides): Fasting venous blood was drawn after overnight fasting of 8-10 hours from both Group A and B patients before the test.

A.   FASTING BLOOD SUGAR:

Plasma fasting sugar was measured by Hexokinase method using Cobas 600 machine

B.    SERUM HDL CHOLESTEROL:

Serum HDL Cholesterol was measured by HDL direct method using Cobas 600 machine

C.   SERUM TRIGLYCERIDES:

Serum Triglycerides was measured by GPO,POD method using Cobas 600 machine

DEFINING CRITERIA:

The presence of Syndrome X was defined by presence of 3 or more positive parameters out of five in the below mentioned criteria’s as per the recent definition from Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity and a Consensus Statement for Diagnosis of Obesity, Abdominal Obesity and the Metabolic Syndrome for Asian Indians^20,21:

1.     WAIST CIRCUMFERENCE:≥90cms in males and ≥80cms in females

2.     BLOOD PRESSURE: Systolic blood pressure≥130 mm Hg or Diastolic blood pressure ≥85 mm Hg or on any Antihypertensive medication

3.     SERUM FASTING GLUCOSE:≥100mg/100ml or on any drug treatment for Diabetes mellitus

4.     SERUM TRIGLYCERIDES: ≥150mg/100ml or on treatment for lipid disorders

5.     SERUM HDL CHOLESTEROL: <40mg/100ml in males and <50mg/100ml in females or on treatment for high cholesterol

·        If the patient was diagnosed with Syndrome X, health education will be given. This will include explaining the patient to adopt certain preventive measures such as lifestyle modifications, exercises, and healthy diet to combat Syndrome X and its complications.